The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index; none of the 14 sources its claims cite is checked for support yet.
A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis
Open accessAbstract
The incidence of tuberculosis has been increasing substantially on a worldwide basis over the past decade, but no tuberculosis-specific drugs have been discovered in 40 years. We identified a diarylquinoline, R207910, that potently inhibits both drug-sensitive and drug-resistant Mycobacterium tuberculosis in vitro (minimum inhibitory concentration 0.06 mug/ml). In mice, R207910 exceeded the bactericidal activities of isoniazid and rifampin by at least 1 log unit. Substitution of drugs included in the World Health Organization's first-line tuberculosis treatment regimen (rifampin, isoniazid, and pyrazinamide) with R207910 accelerated bactericidal activity, leading to complete culture conversion after 2 months of treatment in some combinations. A single dose of R207910 inhibited mycobacterial growth for 1 week. Plasma levels associated with efficacy in mice were well tolerated in healthy human volunteers. Mutants selected in vitro suggest that the drug targets the proton pump of adenosine triphosphate (ATP) synthase.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
52 Own result · 16 Own interpretation · 13 No basis given · 9 Sources not found · 1 Own method
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“R207910 was extensively distributed to tissues, including lungs and spleen (Fig. 3A, table S4).”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Chemistry and in vitro anti-mycobacterial activity.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These average concentrations were greater than that achieving optimal activity in established infection in mice.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Pharmacodynamic studies in mice.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Low MICs were also found for other mycobacterial species, including Mycobacterium bovis, Mycobacterium kansasii and Mycobacterium ulcerans, as well as species naturally resistant to many other anti-TB agents and involved in opportunistic infections, such as Mycobacterium avium complex (MAC), Mycobacterium abscessus, Mycobacterium fortuitum and Mycobacterium marinum (Table 1).”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Chemistry and in vitro anti-mycobacterial activity.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At 25 mg/kg, the activity of R207910 was significantly better than at 12.5 mg/kg (P = 0.005).”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Pharmacodynamic studies in mice.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The bactericidal activity obtained by the RHZ combination after 2 months of therapy was matched by the combinations JHZ and RJZ after just 1 month of therapy.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Pharmacodynamic studies in mice.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Importantly, at 12.5 and 25 mg/kg, R207910 was significantly more active (P = 0.005) than 25 mg/kg isoniazid, a drug known for its strong, early bactericidal activity (Fig. 4A).”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Pharmacodynamic studies in mice.
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition, the susceptibility of R207910-resistant M. tuberculosis strains remained unchanged to other anti-TB agents, including isoniazid, rifampin, streptomycin, amikacin, ethambutol and moxifloxacin.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Chemistry and in vitro anti-mycobacterial activity.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“To date, 20 molecules of the DARQ series have a minimum inhibitory concentration (MIC) below 0.5 µg/ml against M. tuberculosis H37Rv.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Chemistry and in vitro anti-mycobacterial activity.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Data from a multiple-ascending-dose study have shown an increase (approximately by a factor of two) in AUC 0-24h from Day 1 to Day 14 of once-daily dosing at 50, 150 and 400 mg R207910, without substantial variation between subjects.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Pharmacodynamic studies in mice.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Plasma levels associated with efficacy in mice are well tolerated in healthy human volunteers.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Safety and tolerability in humans.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
- Probably not a substantial claim. 3
- It may state two separate claims as one. 40
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The most active compound of the class, R207910, is a pure enantiomer with two chiral centers.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Chemistry and in vitro anti-mycobacterial activity.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“No accumulation of R207910 was observed after five daily oral doses, indicating that slow redistribution from tissues contributed to the relatively long half-lives in plasma.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Chemistry and in vitro anti-mycobacterial activity.
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the second study, the good tolerability was maintained; only one subject withdrew from the study, because of a urinary tract infection (unrelated to R207910) after seven doses at 150 mg/day.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Safety and tolerability in humans.
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“When added to the first-line triple TB therapy combination RHZ, 25 mg/kg R207910 (J) increased the drop in bacterial load in the lungs by 2 log 10 after 1 month of therapy compared with standard RHZ treatment regimen, and a further 1 log 10 drop after 2 months.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Pharmacodynamic studies in mice.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Maximum plasma concentrations (C max ) of 0.40-0.54µg/ml with a single 6.25 mg/kg/dose were achieved within 1 hour and 1.1-1.3µg/ml with a 25 mg/kg/dose within 2-4 hours.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Chemistry and in vitro anti-mycobacterial activity.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The majority of adverse events reported (supporting online text), were considered possibly related to the study medication-placebo (seven of 18 subjects) or R207910 (20 of 36 subjects).”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Safety and tolerability in humans.
plainconditionaln = 36- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The AUC showed a better correlation with the dose than C max , reflecting limitations in rate of absorption at higher dosing regimens, as confirmed in a single-dose pharmacokinetic study comparing C max and AUC after 6.25, 25 and 100 mg/kg.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Chemistry and in vitro anti-mycobacterial activity.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“This anti-mycobacterial-specific spectrum differs from that of isoniazid, which has very poor activity against MAC.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Safety and tolerability in humans.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In studies using oral treatment of R207910 for 5 days per week for 4 weeks, starting the day after inoculation, the minimal dose of R207910 that prevented mortality in nonestablished infection was 1.5 mg/kg, and the minimal effective dose (MED) preventing gross lung lesions was 6.5 mg/kg.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Pharmacodynamic studies in mice.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Exposure of M. tuberculosis in log-phase growth to concentrations of R207910 at 10-fold MIC resulted in a 3 log 10 reduction in bacterial counts after 12 days, indicating that R207910 has bactericidal activity in vitro (table S2).”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Chemistry and in vitro anti-mycobacterial activity.
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Complementation studies have verified that the mutant atpE gene is responsible for resistance to R207910, implying that the atpE gene product is the target of R207910 in mycobacteria.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Chemistry and in vitro anti-mycobacterial activity.
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The range of MICs for the international reference strain M. tuberculosis H37Rv and six fully antibiotic susceptible isolates was 0.03-0.120µg/ml (Table 1), versus 0.500 µg/ml for rifampin and 0.120 µg/ml for isoniazid (results not shown).”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Chemistry and in vitro anti-mycobacterial activity.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“All 30 isolates of MDR-TB tested were susceptible to 0.100 µg/ml of R207910, and 17 (57%) were susceptible to 0.010 µg/ml of R207910 (Table 2).”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Chemistry and in vitro anti-mycobacterial activity.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Pharmacokinetic results from the single-ascending-dose study suggested that R207910 is well absorbed after single oral administration, and the peak concentration was reached at 5 hours (median value) post-dose.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Pharmacodynamic studies in mice.
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“R207910 had much higher MICs for Corynebacterium and Helicobacter pylori (MIC 4.0 µg/ml), and especially for other organisms such as Gram-positive Nocardia, Streptococcus pneumoniae, Staphylococcus aureus and Enterococcus faecalis, or Gram-negative Escherichia coli and Haemophilus influenzae (table S1).”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Chemistry and in vitro anti-mycobacterial activity.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Half-lives ranged from 43.7 to 64 hours in plasma and 28.1 to 92 hours in tissues (table S4).”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Chemistry and in vitro anti-mycobacterial activity.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Substitution of drugs included in the World Health Organization's firstline tuberculosis treatment regimen (rifampin, isoniazid and pyrazinamide) with R207910 accelerates bactericidal activity, leading to complete culture conversion after 2 months of treatment in some combinations.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Safety and tolerability in humans.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The DARQ R207910 is a member of a new chemical class of anti-mycobacterial agents and has an MIC equal to or lower than that of reference compounds.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Safety and tolerability in humans.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A single dose of 50 mg/kg R207910 in the non-established infection murine model of TB infection resulted in a bacteriostatic effect (0.5 log 10 drop in bacterial count in the lungs), which lasted for 8 days-a similar effect to that of rifapentine (10 mg/kg) (Fig. 3B).”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Pharmacodynamic studies in mice.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In established infection (treatment beginning 12-14 days after inoculation when bacterial load was 5.94 log 10 CFU), 25 mg/kg R207910 as monotherapy was at least as active as the triple combination therapy (rifampin [R] + isoniazid [H] + pyrazinamide [Z]), and more active than rifampin alone (Fig. 4B).”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Pharmacodynamic studies in mice.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We identified a diarylquinoline, R207910, that potently inhibits both drug-sensitive and drug-resistant Mycobacterium tuberculosis in vitro (MIC 0.06 µg/ml).”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Safety and tolerability in humans.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The mean AUC 0-24h values were 7.91, 24 and 52 µg/hour/ml at steady state, corresponding to average concentrations of 0.33, 1.0 and 2.2 µg/ml across a dosing interval, with 50, 150 and 400 mg/day, respectively.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Pharmacodynamic studies in mice.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The pharmacokinetics of R207910 were linear up to the highest dose tested (700 mg); both C max and AUC increased proportionally with the administered dose.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Pharmacodynamic studies in mice.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The two point mutations identified (D32V for M. smegmatis and A63P for M. tuberculosis) are both in the membrane-spanning domain region of the protein.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Chemistry and in vitro anti-mycobacterial activity.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Areas under the concentration-time curve (AUCs) ranged from 5.0 to 5.9 µg/hour/ml with a 6.25 mg/kg/dose and 18.5 to 19.4 µg/hour/ml with a 25 mg/kg/dose (table S4).”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Chemistry and in vitro anti-mycobacterial activity.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“From selection experiments, the proportion of resistant mutants that emerged was 5 x 10 -7 and 2 x 10 -8 at four-fold MIC, and 5 x 10 -8 and 1 x 10 -8 at eight-fold MIC for M. tuberculosis and M. smegmatis, respectively (8).”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Chemistry and in vitro anti-mycobacterial activity.
What the sources say
- Not matchedcites [8] 8. Details of materials and methods and supporting online text are available as supporting material on Science Online.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Substitution of each of the three first-line drugs with R207910 resulted in a dramatic increase in potency, leading to complete culture conversion of the lungs in some animals after only 2 months of treatment.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Safety and tolerability in humans.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“R207910 has potent early bactericidal activity in the nonestablished murine TB model, matching or exceeding that of isoniazid (Fig. 4A), which is consistent with in vitro observations pointing to a bactericidal activity.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Safety and tolerability in humans.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Interestingly, the bactericidal potency seen upon administration of a single dose of 100 mg/kg R207910 in vivo was similar to the effect seen upon continuous exposure of cultures to 0.6 µg/ml (or 10-fold the median MIC of the H37Rv strain) in vitro, giving a first indication of the pharmacodynamics of R207910.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Safety and tolerability in humans.
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, the minimal bactericidal dose was very close to the MED, a finding confirming timedependent, rather than concentration-dependent, activity of R207910 in vitro.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Pharmacodynamic studies in mice.
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Data suggest that maintaining average plasma levels of 0.3 µg/ml/day across a dosing interval, which is achieved with a 100 mg/kg/week dose, is necessary to achieve optimal effect of monotherapy in mice infected with strain H37Rv.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Chemistry and in vitro anti-mycobacterial activity.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The killing effect was not increased by higher concentrations of the compound, suggesting the killing was time-dependent rather than concentration-dependent.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Chemistry and in vitro anti-mycobacterial activity.
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Although current first-line anti-TB drug regimens can achieve more than 99% efficacy, this is often reduced because of drug resistance (5).”
What the sources say
- Not matchedcites [5] 5. R. J. O'Brien, P. P. Nunn, Am. J. Respir. Crit. Care Med. 163, 1055 (2001).
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“Structurally and mechanistically, DARQs are very different from both fluoroquinolones (including methoxyquinolones) and other quinoline classes, including mefloquine and its analogs 4-methylquinolines and 4quinolylhydrazones (9-13).”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Chemistry and in vitro anti-mycobacterial activity.
What the sources say
- Not matchedcites [9] 9. R. Jain, B. Vaitilingam, A. Nayyar, P. B. Palde, Bioorg. Med. Chem. Lett. 13, 1051 (2003).
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [10] 10. C. M. Kunin, W. Y. Ellis, Antimicrob. Agents Chemother. 44, 848 (2000).
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [11] 11. M. R. Barbachyn, S. J. Brickner, Patent (International Publication Number: WO 93/09103, International Publication Date: 13 May, 1993, International Application Number: PCT/US92/08267, International Filing Date: 1992).
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [12] 12. L. Savini, L. Chiasserini, A. Gaeta, C. Pellerano, Bioorg. Med. Chem. 10, 2193 (2002). / www.sciencexpress.org /9 December 2004 / Page 4/ 10.1126/science.1106753
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [13] 13. S. Vangapandu, M. Jain, R. Jain, S. Kaur, P. P. Singh, Bioorg. Med. Chem. 12, 2501 (2004).
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The long half-lives and consequently prolonged exposure are important factors determining the duration of activity in vivo and provide a rationale for less frequent dosing regimens.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Chemistry and in vitro anti-mycobacterial activity.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A comparison of the sequences of ATP synthases of different bacteria and of eukaryotic ATP synthase provides a rationale for the specificity of the antibacterial spectrum and, to a lesser extent, the safety profile of R207910.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Safety and tolerability in humans.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, the distinct target of R207910 means that there is no crossresistance with existing anti-TB drugs, and our studies verified it is as effective against MDR strains as it is against fully antibiotic-susceptible strains.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Safety and tolerability in humans.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“Inhibition of ATP synthase function may lead to ATP depletion and imbalance in pH homeostasis, both contributing to decreased survival (15,16).”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Safety and tolerability in humans.
What the sources say
- Not matchedcites [15] 15. M. Rao, T. L. Streur, F. E. Aldwell, G. M. Cook, Microbiology 147, 1017 (2001).
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [16] 16. G. Deckers-Hebestreit, K. Altendorf, Annu. Rev. Microbiol. 50, 791 (1996).
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These are all attributes that are valuable for treatment of chronic infections and they may also be important for the development of simpler dosing regimens.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Safety and tolerability in humans.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“The extent of bacterial load, the most effective drug combinations and treatment duration needed for sterilization are all similar in mice and humans (17).”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Safety and tolerability in humans.
What the sources say
- Not matchedcites [17] 17. E. L. Nuermberger et al., Am. J. Respir. Crit. Care Med. 169, 421 (2004).
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
The paper relies on this without support.
No tuberculosis-specific drugs have been discovered in 40 years.
“Tuberculosis has been increasing significantly on a worldwide basis over the past decade, but no tuberculosisspecific drugs have been discovered in 40 years.”
The paper relies on this without support.
The murine TB model is predictive of human TB treatment outcomes.
“The extent of bacterial load, the most effective drug combinations and treatment duration needed for sterilization are all similar in mice and humans (17).”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“TMC207 is bactericidal towards most species of mycobacteria (109), but is only bacteriostatic against M. avium (118) and M. smegmatis (Berney and Cook, unpublished data).”
From Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria (2014) · cites this paper as [109]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“When mycobacterial cells (growing or non-growing) are treated with TMC207, time-dependent (not dose-dependent) killing is observed (109).”
From Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria (2014) · cites this paper as [109]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The most promising compounds clinically, the diarylquinolines, have been shown to target the F1Fo-ATP synthase and inhibit ATP synthesis (109, 111, 112).”
From Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria (2014) · cites this paper as [109]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“M. smegmatis was used for the initial compound screening that identified diarylquinoline (later named Bedaquiline) as a specific inhibitor of mycobacterial ATP synthase in 2005, which ended a 40-year dearth in anti-TB drug discovery (147).”
From Mycobacterium smegmatis: The Vanguard of Mycobacterial Research (2023) · cites this paper as [147]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Furthermore, Bedaquiline, the first new TB drug in 40 years, was discovered through an M. smegmatis screen.”
From Mycobacterium smegmatis: The Vanguard of Mycobacterial Research (2023) · cites this paper as [147]
Citations
Cites
Amino acid substitution matrices from protein blocks.
Henikoff, S., & Henikoff, J. G. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.22.10915 · Cited by 6,218
The Growing Burden of Tuberculosis: Global Trends and Interactions With the HIV Epidemic
Corbett, E. L., Watt, C. J., Walker, N., Maher, D., Williams, B. G., Raviglione, M. C., & Dye, C. (2003) · Archives of Internal Medicine · doi:10.1001/archinte.163.9.1009 · Cited by 2,553
A systematic review of the associations between dose regimens and medication compliance
Claxton, A. J., Cramer, J., & Pierce, C. (2001) · Clinical Therapeutics · doi:10.1016/s0149-2918(01)80109-0 · Cited by 2,388
Comparing the Means of Several Groups
Godfrey, K. (1985) · New England Journal of Medicine · doi:10.1056/nejm198512053132305 · Cited by 740
Moxifloxacin-containing Regimen Greatly Reduces Time to Culture Conversion in Murine Tuberculosis
Nuermberger, E. L., Yoshimatsu, T., Tyagi, S. K., et al. (2003) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200310-1380oc · Cited by 315
Evaluation of rapid radiometric method for drug susceptibility testing of Mycobacterium tuberculosis
Siddiqi, S. H., Libonati, J. P., & Middlebrook, G. (1981) · Journal of Clinical Microbiology · doi:10.1128/jcm.13.5.908-912.1981 · Cited by 242
The Need for New Drugs against Tuberculosis
O'BRIEN, R. J., & NUNN, P. P. (2001) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.163.5.2007122 · Cited by 221
THE F0F1-TYPE ATP SYNTHASES OF BACTERIA: Structure and Function of the F0 Complex
Deckers-Hebestreit, G., & Altendorf, K. (1996) · Annual Review of Microbiology · doi:10.1146/annurev.micro.50.1.791 · Cited by 195
Intracellular pH regulation by Mycobacterium smegmatis and Mycobacterium bovis BCG
Rao, M., Streur, T. L., Aldwell, F. E., & Cook, G. M. (2001) · Microbiology · doi:10.1099/00221287-147-4-1017 · Cited by 148
Synthesis and anti-tubercular evaluation of 4-quinolylhydrazones
Savini, L., Chiasserini, L., Gaeta, A., & Pellerano, C. (2002) · Bioorganic & Medicinal Chemistry · doi:10.1016/s0968-0896(02)00071-8 · Cited by 134
Cited by
Sorted by citations
Griffith, D. E., Aksamit, T., Brown-Elliott, B. A., Catanzaro, A., Daley, C., Gordin, F., Holland, S. M., Horsburgh, R., Huitt, G., Iademarco, M. F., et al. (2007) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200604-571st · Cited by 6,110
Drugs for bad bugs: confronting the challenges of antibacterial discovery
Payne, D. J., Gwynn, M. N., Holmes, D. J., & Pompliano, D. L. (2007) · Nature Reviews Drug Discovery · doi:10.1038/nrd2201 · Cited by 2,512
“pneumoniae to the atpC subunit of theF 0 F 1 ATPase, a target limited in essentiality to selected pathogens including some streptococci and Mycobacterium tuberculosis”
BackgroundAn integrated semiconductor device enabling non-optical genome sequencing
Rothberg, J. M., Hinz, W., Rearick, T. M., Schultz, J., Mileski, W., Davey, M. S., Leamon, J. H., Johnson, K., Milgrew, M. J., Edwards, M. M., et al. (2011) · Nature · doi:10.1038/nature10242 · Cited by 2,271
The impact of next-generation sequencing technology on genetics
Mardis, E. R. (2008) · Trends in Genetics · doi:10.1016/j.tig.2007.12.007 · Cited by 2,113
“A remarkable study by an international consortium used 454 sequencing of Mycobacterium tuberculosis to identify drug targets of a diarylquinoline drug that potently inhibited both drugsensitive and -resistant strains of the pathogen [ 21 ].”
BackgroundAntibiotics and Bacterial Resistance in the 21st Century
Fair, R. J., & Tor, Y. (2014) · Perspectives in Medicinal Chemistry · doi:10.4137/pmc.s14459 · Cited by 2,041
Next-generation sequencing transforms today's biology
Schuster, S. C. (2007) · Nature Methods · doi:10.1038/nmeth1156 · Cited by 1,870
Antibiotics for Emerging Pathogens
Fischbach, M. A., & Walsh, C. T. (2009) · Science · doi:10.1126/science.1176667 · Cited by 1,787
Platforms for antibiotic discovery
Lewis, K. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd3975 · Cited by 1,527
The spectrum of latent tuberculosis: rethinking the biology and intervention strategies
Barry, C. E., Boshoff, H. I., Dartois, V. A., Dick, T., Ehrt, S., Flynn, J. L., Schnappinger, D., Wilkinson, R. J., & Young, D. B. (2009) · Nature Reviews Microbiology · doi:10.1038/nrmicro2236 · Cited by 1,441
“Subsequent identification of the mechanism of action of active compounds is achieved by sequencing the genome of spontaneous drug-resistant mutant”
Pai, M., Behr, M. A., Dowdy, D., Dheda, K., Divangahi, M., Boehme, C. C., Ginsberg, A., Swaminathan, S., Spigelman, M., Getahun, H., et al. (2016) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2016.76 · Cited by 1,270
The challenge of new drug discovery for tuberculosis
Koul, A., Arnoult, É., Lounis, N., Guillemont, J., & Andries, K. (2011) · Nature · doi:10.1038/nature09657 · Cited by 1,063
Self-citationOpportunities and challenges in phenotypic drug discovery: an industry perspective
Moffat, J. G., Vincent, F., Lee, J. A., Eder, J., & Prunotto, M. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.111 · Cited by 939
Advances in the development of new tuberculosis drugs and treatment regimens
Zumla, A. I., Nahid, P., & Cole, S. T. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4001 · Cited by 921
Hurdle, J. G., O’Neill, A. J., Chopra, I., & Lee, R. E., Jr. (2010) · Nature Reviews Microbiology · doi:10.1038/nrmicro2474 · Cited by 890
“TMC207 specifically binds to subunit C of the mycobacterial F 0 F 1 -ATPase, sterically blocking the enzyme's rotational motor and thereby inhibiting proton translocation and coupled ATP biosynthesi”
The Diarylquinoline TMC207 for Multidrug-Resistant Tuberculosis
Diacon, A. H., Pym, A. S., Grobusch, M. P., Patientia, R. F., Rustomjee, R., Page‐Shipp, L., Pistorius, C., Krause, R., Bogoshi, M., Churchyard, G., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0808427 · Cited by 841
“Unilateral 3 (13) 5 (21) Bilateral 2 ( 9 ) 3 (12)”
InfluentialSelf-citationMycobacterium abscessus: a new antibiotic nightmare
Nessar, R., Cambau, E., Reyrat, J., Murray, A., & Gicquel, B. (2012) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkr578 · Cited by 800
Self-citationThe Science of Antibiotic Discovery
Lewis, K. (2020) · Cell · doi:10.1016/j.cell.2020.02.056 · Cited by 848
Antibiotic efficacy is linked to bacterial cellular respiration
Lobritz, M. A., Belenky, P. A., Porter, C. B. M., Gutierrez, A., Yang, J. H., Schwarz, E. G., Dwyer, D. J., Khalil, A. S., & Collins, J. J. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1509743112 · Cited by 775
“The F1F0 ATPase is the target of bedaquiline, a novel antibiotic for the treatment of tuberculosis (50, 51).”
BackgroundMultidrug-Resistant Tuberculosis and Culture Conversion with Bedaquiline
Diacon, A. H., Pym, A. S., Grobusch, M. P., Ríos, J. D. L., Gotuzzo, E., Vasilyeva, I. A., Leimane, V., Andries, K., Bakare, N., Marez, T. D., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1313865 · Cited by 751
Self-citationBenzothiazinones Kill Mycobacterium tuberculosis by Blocking Arabinan Synthesis
Makarov, V., Manina, G., Mikusova, K., Möllmann, U., Ryabova, O., Saint-Joanis, B., Dhar, N., Pasca, M. R., Buroni, S., Lucarelli, A. P., et al. (2009) · Science · doi:10.1126/science.1171583 · Cited by 740
Gagneux, S., & Small, P. M. (2007) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(07)70108-1 · Cited by 729
New antibiotics from bacterial natural products
Clardy, J., Fischbach, M. A., & Walsh, C. T. (2006) · Nature Biotechnology · doi:10.1038/nbt1266 · Cited by 619
“The synthetic diarylquinolones that have been recently reported by Johnson & Johnson's (Beerse, Belgium) Andries et al”
BackgroundDiscovery of Q203, a potent clinical candidate for the treatment of tuberculosis
Pethe, K., Bifani, P. J., Jang, J., Kang, S., Park, S., Ahn, S., Jiřiček, J., Jung, J., Jeon, H. K., Cechetto, J. D., et al. (2013) · Nature Medicine · doi:10.1038/nm.3262 · Cited by 601
High Functional Diversity in Mycobacterium tuberculosis Driven by Genetic Drift and Human Demography
Hershberg, R., Lipatov, M., Small, P. M., Sheffer, H., Niemann, S., Homolka, S., Roach, J. C., Kremer, K., Petrov, D. A., Feldman, M. W., et al. (2008) · PLoS Biology · doi:10.1371/journal.pbio.0060311 · Cited by 613
“], as well as genes of special interest, including putative new drug targets [”
BackgroundDiarylquinolines target subunit c of mycobacterial ATP synthase
Koul, A., Dendouga, N., Vergauwen, K., Molenberghs, B., Vranckx, L., Willebrords, R., Ristic, Z., Lill, H., Dorange, I., Guillemont, J., et al. (2007) · Nature Chemical Biology · doi:10.1038/nchembio884 · Cited by 547
Self-citationRao, S. P. S., Alonso, S., Rand, L., Dick, T., & Pethe, K. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0711697105 · Cited by 517
“R207910 reduces the time of therapy in animal models (15, 28) and shows superior sterilization activity compared with standard anti-TB drugs.”
BackgroundMethodInfluentialDye, C. (2005) · JAMA · doi:10.1001/jama.293.22.2767 · Cited by 537
“The ultimate tool, yet to be created, is a vaccine that has consistently high efficacy against pulmonary TB, whether or not vaccinated individuals are already infected.(49,50) In any discussion of TB control, it is vital to remember that incidence and death rates are not governed simply by drug treatment.”
Backgroundda Silva, P. E. A., & Palomino, J. C. (2011) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkr173 · Cited by 548
The development and impact of 454 sequencing
Rothberg, J. M., & Leamon, J. H. (2008) · Nature Biotechnology · doi:10.1038/nbt1485 · Cited by 561
“To demonstrate the potential for whole-genome sequencing, and with methods and software both in place, one of the earliest collaborations was a project in which four genomes were sequenced to determine the mechanism of resistance to the drug R207910 in Mycobacterium tuberculosis”
MethodPyrazinamide Inhibits Trans-Translation in Mycobacterium tuberculosis
Shi, W., Zhang, X., Jiang, X., Yuan, H., Lee, J. S., Barry, C. E., Wang, H., Zhang, W., & Zhang, Y. (2011) · Science · doi:10.1126/science.1208813 · Cited by 516
Hartkoorn, R. C., Uplekar, S. M., & Cole, S. T. (2014) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00037-14 · Cited by 493
“In previous work with bedaquiline-resistant H37Rv mutants isolated in vitro, it was found that 15 out of 53 resistant mutants carried mutations in atpE, the gene that encodes the target subunit of bedaquiline in ATP synthase (15, 16).”
BackgroundTargeting Antibiotic Resistance
Chellat, M. F., Raguž, L., & Riedl, R. (2016) · Angewandte Chemie International Edition · doi:10.1002/anie.201506818 · Cited by 505
Antituberculosis drugs: Ten years of research
Janin, Y. L. (2007) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2007.01.030 · Cited by 483
Microbial Persistence and the Road to Drug Resistance
Cohen, N. R., Lobritz, M. A., & Collins, J. J. (2013) · Cell Host & Microbe · doi:10.1016/j.chom.2013.05.009 · Cited by 475
“Indeed, inhibition of the mycobacterial proteasome or ATP synthase has been shown to promote the death of nongrowing M. tuberculosis (Andries et al., 2005; Gandotra et al., 2007; Lin et al., 2009).”
BackgroundTreatment of Drug-Resistant Tuberculosis. An Official ATS/CDC/ERS/IDSA Clinical Practice Guideline
Nahid, P., Mase, S., Migliori, G. B., Sotgiu, G., Bothamley, G. H., Brożek, J., Cattamanchi, A., Cegielski, J. P., Chen, L., Daley, C. L., et al. (2019) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201909-1874st · Cited by 463
“Bedaquiline is bactericidal to nonreplicating and actively replicating mycobacteria, through ATP synthase inhibition, and has bactericidal and sterilizing activity in the murine model of TB infection (73).”
BackgroundDrug Resistance Mechanisms in Mycobacterium tuberculosis
Palomino, J. C., & Martin, A. (2014) · Antibiotics · doi:10.3390/antibiotics3030317 · Cited by 467
“genome of these mutants and comparing to that of the susceptible strains, the only mutation found was in the atpE gene, which encodes the c part of the F0 subunit of the ATP synthase [117].”
BackgroundShort read fragment assembly of bacterial genomesPreprint
Chaisson, M., & Pevzner, P. A. (2007) · Genome Research · doi:10.1101/gr.7088808 · Cited by 444
“The applications of HTSR sequencing have been largely limited, albeit with great success, to resequencing (Andries et al. 2005), gene expression (Kim et al.”
BackgroundAcquired Resistance of Mycobacterium tuberculosis to Bedaquiline
Andries, K., Villellas, C., Coeck, N., Thys, K., Gevers, T., Vranckx, L., Lounis, N., de Jong, B. C., & Koul, A. (2014) · PLoS ONE · doi:10.1371/journal.pone.0102135 · Cited by 448
“BK12 BDQ-R mutant, H37Rv-derived, atpE mutation [2] no mutation no mutation 2.”
BackgroundSelf-citationYoshida, K., Saitoh, H., Fujisawa, S., Kanzaki, H., Matsumura, H., Yoshida, K., Tosa, Y., Chuma, I., Takano, Y., Win, J., et al. (2009) · The Plant Cell · doi:10.1105/tpc.109.066324 · Cited by 441
Antibiotics in the clinical pipeline in 2013
Butler, M. S., Blaskovich, M. A. T., & Cooper, M. A. (2013) · The Journal of Antibiotics · doi:10.1038/ja.2013.86 · Cited by 436
Mechanisms of action of isoniazid
Timmins, G. S., & Deretic, V. P. (2006) · Molecular Microbiology · doi:10.1111/j.1365-2958.2006.05467.x · Cited by 443
“derivatives (Andries et al., 2005), there remains as much”
BackgroundTowards a new combination therapy for tuberculosis with next generation benzothiazinones
Makarov, V., Lechartier, B., Zhang, M., Neres, J., van der Sar, A. M., Raadsen, S. A., Hartkoorn, R. C., Riabova, O., Vocat, A., Decosterd, L. A., et al. (2014) · EMBO Molecular Medicine · doi:10.1002/emmm.201303575 · Cited by 391
“As can be seen in Fig 9, the combination of PBTZ169 and BDQ was more effective than the standard treatment in reducing the number of CFU in both organs after 1 month of treatment ( P values = 0.004 for the lung, 0.002 for the spleen) whereas the addition of PZA did not further improve the potency of the combination at…”
InfluentialSelf-citationDiacon, A. H., Donald, P. R., Pym, A. S., Grobusch, M. P., Patientia, R. F., Mahanyele, R., Bantubani, N., Narasimooloo, R., Marez, T. D., van Heeswijk, R., et al. (2012) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.06126-11 · Cited by 371
“TMC207, recently renamed bedaquiline, is a diarylquinoline with a novel mode of action specifically inhibiting mycobacterial ATP synthase (1).”
BackgroundSelf-citationAlvin, A., Miller, K. I., & Neilan, B. A. (2014) · Microbiological Research · doi:10.1016/j.micres.2013.12.009 · Cited by 391
“Drug Sponsor Class In vitro potency Mode of action Clinical trial status TMC 207 (Bedaquiline) Janssen Diarylquinoline 30–120 ng/ml (Andries et al., 2005; Koul et al., 2008) Targeting ATP synthase, inhibition of proton pumping activity (Huitric et al., 2010) III, FDA-approved (accelerated…”
Global tuberculosis drug development pipeline: the need and the reality
Ma, Z., Lienhardt, C., McIlleron, H., et al. (2010) · The Lancet · doi:10.1016/s0140-6736(10)60359-9 · Cited by 374
Diarylquinolines Are Bactericidal for Dormant Mycobacteria as a Result of Disturbed ATP Homeostasis
Koul, A., Vranckx, L., Dendouga, N., Balemans, W., Van den Wyngaert, I., Vergauwen, K., Göhlmann, H. W. H., Willebrords, R., Poncelet, A., Guillemont, J., et al. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m803899200 · Cited by 364
Self-citationProspects for new antibiotics: a molecule-centered perspective
Walsh, C. T., & Wencewicz, T. A. (2013) · The Journal of Antibiotics · doi:10.1038/ja.2013.49 · Cited by 385
Protopopova, M. N., Hanrahan, C. F., Nikonenko, B. V., Samala, R., Chen, P., Gearhart, J., Einck, L., & Nacy, C. A. (2005) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dki319 · Cited by 372
Structure of the Rotor Ring of F-Type Na + -ATPase from Ilyobacter tartaricus
Meier, T. W., Polzer, P., Diederichs, K., Welte, W., & Dimroth, P. (2005) · Science · doi:10.1126/science.1111199 · Cited by 370
Small-Molecule Inhibitor of Vibrio cholerae Virulence and Intestinal Colonization
Hung, D. T., Shakhnovich, E. A., Pierson, E. R., & Mekalanos, J. J. (2005) · Science · doi:10.1126/science.1116739 · Cited by 358
Twenty years of bacterial genome sequencing
Loman, N. J., & Pallen, M. J. (2015) · Nature Reviews Microbiology · doi:10.1038/nrmicro3565 · Cited by 361
Dookie, N., Rambaran, S., Padayatchi, N., Mahomed, S., & Naidoo, K. (2018) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkx506 · Cited by 344
New antituberculosis drugs, regimens, and adjunct therapies: needs, advances, and future prospects
Zumla, A. I., Gillespie, S. H., Höelscher, M., Philips, P. P. J., Cole, S. T., Abubakar, I. I., McHugh, T. D., Schito, M. L., Maeurer, M. J., & Nunn, A. J. (2014) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(13)70328-1 · Cited by 355
The Normalcy of Dormancy: Common Themes in Microbial Quiescence
Rittershaus, E. S. C., Baek, S.-H., & Sassetti, C. M. (2013) · Cell Host & Microbe · doi:10.1016/j.chom.2013.05.012 · Cited by 350
“Bedaquiline inhibits the F0F1 ATP synthase, a function required for energy maintenance (Andries et al., 2005), PA-824 is a nitroimidazole that kills via nonspecific nitrosative (nitrogen radical-mediated) damage (Singh et al., 2008), and moxifloxacin produces DNA breaks at sites of ongoing…”
Robust Salmonella metabolism limits possibilities for new antimicrobials
Becker, D., Selbach, M., Rollenhagen, C., Ballmaier, M., Meyer, T. F., Mann, M., & Bumann, D. (2006) · Nature · doi:10.1038/nature04616 · Cited by 342
Mechanisms of Pyrazinamide Action and Resistance
Zhang, Y., Shi, W., Zhang, W., & Mitchison, D. A. (2014) · Microbiology Spectrum · doi:10.1128/microbiolspec.mgm2-0023-2013 · Cited by 341
“The subsequent observation in 2005 that bedaquiline (or TMC207, a diarylquinoline), an inhibitor of F1F0 ATP synthase, could synergizewithPZAactivity (37)—afinding just likeDCCD synergy with PZA shown earlier in 2003 (30)—provides further support for the model of PZA.”
BackgroundResultInfluentialBedaquiline in the treatment of multidrug- and extensively drug-resistant tuberculosis
Pym, A. S., Diacon, A. H., Tang, S., et al. (2015) · European Respiratory Journal · doi:10.1183/13993003.00724-2015 · Cited by 333
Self-citationWhole-genome sequencing to control antimicrobial resistance
Köser, C. U., Ellington, M. J., & Peacock, S. J. (2014) · Trends in Genetics · doi:10.1016/j.tig.2014.07.003 · Cited by 344
Christophe, T., Jackson, M., Jeon, H. K., Fenistein, D., Contreras-Domínguez, M., Kim, J. C., Genovesio, A., Carralot, J., Ewann, F., Kim, E. H., et al. (2009) · PLoS Pathogens · doi:10.1371/journal.ppat.1000645 · Cited by 325
“to be effective for the development of new antitubercular drugs and have identified compounds with new mechanisms of actions such as TMC207 [25,26].”
InfluentialNew agents for the treatment of drug-resistant Mycobacterium tuberculosis
Hoagland, D. T., Liu, J., Lee, R. B., & Lee, R. E. (2016) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2016.04.026 · Cited by 341
“Through the growth of drug-resistant mutants, it was discovered that the rotor ring of the organism's F0F1 ATP synthase was the target, specifically binding to the c subunit [25].”
BackgroundConfronting the scientific obstacles to global control of tuberculosis
Young, D. B., Perkins, M. D., Duncan, K., & Barry, C. E. (2008) · Journal of Clinical Investigation · doi:10.1172/jci34614 · Cited by 318
Pinard, R., de Winter, A., Sarkis, G. J., Gerstein, M., Tartaro, K. R., Plant, R. N., Egholm, M., Rothberg, J. M., & Leamon, J. H. (2006) · BMC Genomics · doi:10.1186/1471-2164-7-216 · Cited by 320
“Background Continued improvement in sequencing quality, combined with increasingly sophisticated bioinformatic analysis of sequence data, has increased the relevance of whole genome sequencing to many fields of biological science including the pharmaceutical industry, agriculture, national defence and medicine [1].”
Bacterial persisters: molecular mechanisms and therapeutic development
Niu, H., Gu, J., & Zhang, Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01866-5 · Cited by 348
“377 Research has shown that when combined with other agents such as pretomanid and moxi fl ox-acin, bedaquiline effectively eliminates M. tuberculosis in non-replicating persister state.”
BackgroundExtensively drug-resistant tuberculosis
Jassal, M. S., & Bishai, W. R. (2008) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(08)70260-3 · Cited by 318
Shi, L., Sohaskey, C. D., Kana, B. D., Dawes, S., North, R. J., Mizrahi, V., & Gennaro, M. L. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0507850102 · Cited by 301
Lilienkampf, A., Mao, J., Wan, B., Wang, Y., Franzblau, S. G., & Kozikowski, A. P. (2009) · Journal of Medicinal Chemistry · doi:10.1021/jm900003c · Cited by 307
The expanding scope of DNA sequencing
Shendure, J., & Aiden, E. L. (2012) · Nature Biotechnology · doi:10.1038/nbt.2421 · Cited by 308
Hong, S., & Pedersen, P. L. (2008) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00016-08 · Cited by 308
“Also, the mycobacterial species naturally resistant to R207910 contains Met at position 63 in place of a conserved Ala in all sensitive mycobacteria (15, 181, 313).”
BackgroundInfluentialMetabolic principles of persistence and pathogenicity in Mycobacterium tuberculosis
Ehrt, S., Schnappinger, D., & Rhee, K. Y. (2018) · Nature Reviews Microbiology · doi:10.1038/s41579-018-0013-4 · Cited by 303
Quinoline: A promising antitubercular target
Keri, R. S., & Patil, S. A. (2014) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2014.10.007 · Cited by 315
“The results of its clinical trials show that TMC207 may shorten the treatment of TB and be effective in its treatment [43–45].”
BackgroundHistory of antimicrobial drug discovery: Major classes and health impact
Aminov, R. I. (2016) · Biochemical Pharmacology · doi:10.1016/j.bcp.2016.10.001 · Cited by 318
Koul, A., Vranckx, L., Dhar, N., Göhlmann, H. W. H., Özdemir, E., Neefs, J., Schulz, M., Lü, P., Mørtz, E., McKinney, J. D., et al. (2014) · Nature Communications · doi:10.1038/ncomms4369 · Cited by 298
Self-citationPreiß, L., Langer, J. D., Yıldız, Ö., Eckhardt-Strelau, L., Guillemont, J., Koul, A., & Meier, T. W. (2015) · Science Advances · doi:10.1126/sciadv.1500106 · Cited by 305
Self-citationPethe, K., de Sequeira, P. C., Agarwalla, S., Rhee, K. Y., Kuhen, K., Phong, W. Y., Patel, V., Beer, D., Walker, J. R., Duraiswamy, J., et al. (2010) · Nature Communications · doi:10.1038/ncomms1060 · Cited by 286
Challenges in tuberculosis drug research and development
Ginsberg, A. M., & Spigelman, M. (2007) · Nature Medicine · doi:10.1038/nm0307-290 · Cited by 283
Raman, K., Yeturu, K., & Chandra, N. R. (2008) · BMC Systems Biology · doi:10.1186/1752-0509-2-109 · Cited by 280
“AtpE1 (Rv1305) Inhibited by a diarylquinoline drug R207910 in vitro [109] 4 4 4 4 4 4 4 Cyp121 (Rv2276) Putative essential gene.”
Rustomjee, R., Diacon, A. H., Allen, J., Venter, A., Reddy, C., Patientia, R. F., Mthiyane, T., Marez, T. D., van Heeswijk, R., Kerstens, R., et al. (2008) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01204-07 · Cited by 279
“The most impressive activity of TMC207 in animal models was observed after treatment for at least 1 month in studies conducted in mice infected with drug-sensitive TB and nonestablished (2) and established infection (2, 12) or MDR-TB (19).”
BackgroundInfluentialNTM drug discovery: status, gaps and the way forward
Wu, M.-L., Aziz, D. B., Dartois, V. A., & Dick, T. (2018) · Drug Discovery Today · doi:10.1016/j.drudis.2018.04.001 · Cited by 291
“Of note, similar to clofazimine which targets type II NADH-quinone oxidoreductase (NDH-2) [51], a key component in the electron transport chain, bedaquiline also targets oxidative phosphorylation via inhibiting ATP synthase [52].”
BackgroundOligomycin Frames a Common Drug-Binding Site in the ATP Synthase
Symersky, J., Osowski, D., Walters, D. E., & Mueller, D. M. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1207912109 · Cited by 269
“Strains resistant against R207910 were isolated, and three independent mutations in the gene encoding subunit-c, Asp26Val, Ala61Pro, Ile64Met (yeast numbering system), were identified as being responsible for conferring resistance to the drug (25, 27).”
BackgroundAntibiotics in the clinical pipeline in 2011
Butler, M. S., & Cooper, M. A. (2011) · The Journal of Antibiotics · doi:10.1038/ja.2011.44 · Cited by 278
Targeting Persisters for Tuberculosis Control
Zhang, Y., Yew, W. W., & Barer, M. R. (2012) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.06288-11 · Cited by 276
“Besides the wellknown strong synergy between PZA and TMC207 (2, 35), a recent study has shown that adding clofazimine could further enhance the synergy of PZA and TMC207 in mice (72).”
BackgroundThe Concept of an Ideal Antibiotic: Implications for Drug Design
Gajdács, M. (2019) · Molecules · doi:10.3390/molecules24050892 · Cited by 275
“Species-selective platform • Screening against a specific bug, resulting in compounds that act selectively against that pathogen [56] • Requires a target that is innate and specific to microorganism • Lower probability of toxicity in the human host • New compounds will not affect commensals in the gut [57] Bedaquiline…”
BackgroundGengenbacher, M., Rao, S. P. S., Pethe, K., & Dick, T. (2009) · Microbiology · doi:10.1099/mic.0.033084-0 · Cited by 270
“Moxifloxacin was obtained from Chempacific and the compound TMC207 was synthesized as described elsewhere (Andries et al., 2005).”
BackgroundMethodDrugs versus bugs: in pursuit of the persistent predator Mycobacterium tuberculosis
Sacchettini, J. C., Rubin, E. J., & Freundlich, J. S. (2007) · Nature Reviews Microbiology · doi:10.1038/nrmicro1816 · Cited by 255
Location of Persisting Mycobacteria in a Guinea Pig Model of Tuberculosis Revealed by R207910
Lenaerts, A. J. M., Hoff, D. R., Aly, S., Ehlers, S., Andries, K., Cantarero, L., Orme, I. M., & Basaraba, R. J. (2007) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00276-07 · Cited by 262
“pyl- -cyclodextrin solution as described before (2).”
BackgroundInfluentialSelf-citationNew Drugs against Tuberculosis: Problems, Progress, and Evaluation of Agents in Clinical Development
van den Boogaard, J., Kibiki, G. S., Kisanga, E. R., Boeree, M. J., & Aarnoutse, R. E. (2008) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00749-08 · Cited by 257
“120 g/ml in both fully susceptible and MDR strains (4, 59).”
BackgroundInfluentialStanley, S. A., Grant, S. S., Kawate, T., Iwase, N., Shimizu, M., Wivagg, C. N., Silvis, M. R., Kazyanskaya, E., Aquadro, J. A., Golas, A. J., et al. (2012) · ACS Chemical Biology · doi:10.1021/cb300151m · Cited by 252
Drug resistant Tuberculosis: A review
Khawbung, J. L., Nath, D., & Chakraborty, S. (2020) · Comparative Immunology Microbiology and Infectious Diseases · doi:10.1016/j.cimid.2020.101574 · Cited by 252
21st Century natural product research and drug development and traditional medicines
Ngô, L., Okogun, J. I., & Folk, W. R. (2013) · Natural Product Reports · doi:10.1039/c3np20120a · Cited by 254
Buruli Ulcer (M. ulcerans Infection): New Insights, New Hope for Disease Control
Johnson, P. D. R., Stinear, T. P., Small, P. L. C., et al. (2005) · PLoS Medicine · doi:10.1371/journal.pmed.0020108 · Cited by 248
Maartens, G., & Wilkinson, R. J. (2007) · The Lancet · doi:10.1016/s0140-6736(07)61262-8 · Cited by 263
Wang, Y., Chen, C., Peng, J., et al. (2013) · Angewandte Chemie International Edition · doi:10.1002/anie.201300586 · Cited by 241
Droege, M., & Hill, B. (2008) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2008.03.021 · Cited by 244
Identification of New Drug Targets and Resistance Mechanisms in Mycobacterium tuberculosis
Ioerger, T. R., O’Malley, T., Liao, R., Guinn, K. M., Hickey, M. J., Mohaideen, N., Murphy, K. C., Boshoff, H. I., Mizrahi, V., Rubin, E. J., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0075245 · Cited by 247
“Bedaquiline) at Johnson & Johnson [4,5].”
Naphthalene, a versatile platform in medicinal chemistry: Sky-high perspective
Makar, S., Saha, T., & Singh, S. K. (2018) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2018.10.018 · Cited by 254
Persisters, persistent infections and the Yin–Yang model
Zhang, Y. (2014) · Emerging Microbes & Infections · doi:10.1038/emi.2014.3 · Cited by 234
Bedaquiline: a review of human pharmacokinetics and drug-drug interactions
van Heeswijk, R. P. G., Dannemann, B. R., & Hoetelmans, R. M. W. (2014) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dku171 · Cited by 240
Why Is Long-Term Therapy Required to Cure Tuberculosis?
Connolly, L. E., Edelstein, P. H., & Ramakrishnan, L. (2007) · PLoS Medicine · doi:10.1371/journal.pmed.0040120 · Cited by 236
“]. Promising candidates under investigation include the ATP synthase inhibitor R207910 [”
BackgroundCingolani, G., & Duncan, T. M. (2011) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2058 · Cited by 227
“Most MF 1 structures are similar to the 1.9 Å ground-state of MF 15 : β 1 and β 3 are each in a ‘closed’ state with bound nucleotide, but β 2 has an open state without nucleotide, since contacts of its CTD with a convex surface of γ distort the nucleotide binding site 4 .”
InfluentialBactericidal mode of action of bedaquiline
Hards, K., Robson, J. R., Berney, M., Shaw, L. E., Bald, D., Koul, A., Andries, K., & Cook, G. M. (2015) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkv054 · Cited by 237
Self-citation
Metadata
- Authors
- Andries, K., Verhasselt, P., Guillemont, J., Göhlmann, H. W. H., Neefs, J.-M., Winkler, H., Van Gestel, J., Timmerman, P., Zhu, M., Lee, E., Williams, P., de Chaffoy, D., Huitric, E., Hoffner, S., Cambau, E., Truffot-Pernot, C., Lounis, N., & Jarlier, V.
- Affiliations
- Johnson & Johnson (United Kingdom) (GB)
- Johnson & Johnson Pharmaceutical Research and Development, Turnhoutseweg 30, 2340 Beerse, Belgium.
- Corresponding author
- Andries, Koen
- Lounis, Nacer
- Venue
- Science
- Published
- 2005-01-14
- Volume
- 307
- Issue
- 5707
- Pages
- 223-227
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2158658436
- Cited by
- 2,191
- References
- 13
- Citations by year
- 2026: 63 · 2025: 98 · 2024: 103 · 2023: 106 · 2022: 111 · 2021: 98 · 2020: 136 · 2019: 141 · 2018: 102 · 2017: 124 · 2016: 120 · 2015: 129 · 2014: 140 · 2013: 106 · 2012: 102
- FWCI
- 27.67
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer therapeutics and mechanisms
- Keywords
- diarylquinolines, Mycobacterium tuberculosis, tuberculosis drug resistance, ATP synthase inhibition, proton pump, bactericidal activity, combination therapy, isoniazid
- MeSH terms
- Amino Acid Sequence, Animals, Antitubercular Agents, Dose-Response Relationship, Drug, Drug Evaluation, Preclinical, Drug Therapy, Combination
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-11, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-11 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
