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
Items 401–500 of 2,159
Bedaquiline-Resistant Tuberculosis: Dark Clouds on the Horizon
Andres, S., Merker, M., Heyckendorf, J., et al. (2020) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201909-1819le · Cited by 79
Novel targets in M. tuberculosis: search for new drugs
Lamichhane, G. (2010) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2010.10.004 · Cited by 81
Structure-Based Design of DevR Inhibitor Active against NonreplicatingMycobacterium tuberculosis
Gupta, R. K., Thakur, T. S., Desiraju, G. R., & Tyagi, J. S. (2009) · Journal of Medicinal Chemistry · doi:10.1021/jm900358q · Cited by 79
Population Pharmacokinetics of Bedaquiline (TMC207), a Novel Antituberculosis Drug
McLeay, S. C., Vis, P., van Heeswijk, R. P. G., et al. (2014) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01418-13 · Cited by 79
“Bedaquiline (formerly TMC207) is a diarylquinoline and novel antimycobacterial agent (5) that was recently approved by the FDA for the treatment of pulmonary MDR-TB in adults, in combination with other agents.”
BackgroundPavan, F. R., Poelhsitz, G. V., Barbosa, M. I. F., et al. (2011) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2011.08.023 · Cited by 79
Azzali, E., Machado, D., Kaushik, A., Vacondio, F., Flisi, S., Cabassi, C. S., Lamichhane, G., Viveiros, M., Costantino, G., & Pieroni, M. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b00793 · Cited by 80
The Expanding Diversity of Mycobacterium tuberculosis Drug Targets
Wellington, S., & Hung, D. T. (2018) · ACS Infectious Diseases · doi:10.1021/acsinfecdis.7b00255 · Cited by 81
Single-Cell Tracking Reveals Antibiotic-Induced Changes in Mycobacterial Energy Metabolism
Maglica, Ž., Özdemir, E., & McKinney, J. D. (2015) · mBio · doi:10.1128/mbio.02236-14 · Cited by 77
“smegmatis (4), a nonpathogenic relative of M.”
BackgroundMethodInfluentialSkin and Soft Tissue Infections Due to Nontuberculous Mycobacteria
Misch, E. A., Saddler, C. M., & Davis, J. M. (2018) · Current Infectious Disease Reports · doi:10.1007/s11908-018-0611-3 · Cited by 81
Sachan, R. S. K., Mistry, V., Dholaria, M., Rana, A., Devgon, I., Ali, I., Javed Iqbal, M., Eldin, S. M., Al-Tawaha, A. R., Bawazeer, S., et al. (2023) · ACS Omega · doi:10.1021/acsomega.3c02563 · Cited by 85
Structure–activity relationships of 2-aminothiazoles effective against Mycobacterium tuberculosis
Meissner, A., Boshoff, H. I., Vasan, M., et al. (2013) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2013.08.048 · Cited by 78
Quinoline and quinolones: promising scaffolds for future antimycobacterial agents
Singh, S., Kaur, G., Mangla, V., et al. (2014) · Journal of Enzyme Inhibition and Medicinal Chemistry · doi:10.3109/14756366.2014.930454 · Cited by 78
“J Enzyme Inhib Med Chem, 2015; 30(3): 492–504 ! 2014 Informa UK Ltd.”
Scherman, M. S., North, E. J., Jones, V. M., Hess, T., Grzegorzewicz, A. E., Kasagami, T., Kim, I.-H., Merzlikin, O., Lenaerts, A. J. M., Lee, R. E., Jr., et al. (2012) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2012.03.058 · Cited by 77
Mycobacterium Tuberculosis: Drug Resistance and Future Perspectives
Riccardi, G., Pasca, M. R., & Buroni, S. (2009) · Future Microbiology · doi:10.2217/fmb.09.20 · Cited by 77
Current development and future prospects in chemotherapy of tuberculosis
Nuermberger, E. L., Spigelman, M., & Yew, W. W. (2010) · Respirology · doi:10.1111/j.1440-1843.2010.01775.x · Cited by 75
Mycobacterial Cell Wall Synthesis Inhibitors Cause Lethal ATP Burst
Shetty, A., & Dick, T. (2018) · Frontiers in Microbiology · doi:10.3389/fmicb.2018.01898 · Cited by 76
Reddyrajula, R., Dalimba, U., & Kumar, S. M. (2019) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2019.02.010 · Cited by 76
New Drugs for Tuberculosis: Current Status and Future Prospects
O'Brien, R. J., & Spigelman, M. (2005) · Clinics in Chest Medicine · doi:10.1016/j.ccm.2005.02.013 · Cited by 76
“tuberculosis and seem promising in an animal model [49].”
BackgroundChang, K. C., & Yew, W.-W. (2012) · Respirology · doi:10.1111/j.1440-1843.2012.02257.x · Cited by 75
Gupta, S., Tyagi, S. K., & Bishai, W. R. (2014) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.04019-14 · Cited by 75
Re-Understanding the Mechanisms of Action of the Anti-Mycobacterial Drug Bedaquiline
Sarathy, J. P., Grüber, G., & Dick, T. (2019) · Antibiotics · doi:10.3390/antibiotics8040261 · Cited by 84
“Furthermore, susceptibility testing of TBAJ-876 against engineered M. smegmatis strains, either over-expressing the ε-subunit or harboring an amino acid alteration at the ε-subunit W16 amino acid residue, showed similar MIC shifts observed for BDQ.”
BackgroundResultInfluentialKumar, K., Daley, C. L., Griffith, D. E., & Loebinger, M. R. (2022) · European Respiratory Review · doi:10.1183/16000617.0212-2021 · Cited by 80
Clp-targeting BacPROTACs impair mycobacterial proteostasis and survival
Hoi, D. M., Junker, S., Junk, L., Schwechel, K., Fischel, K., Podlesainski, D., Hawkins, P. M. E., van Geelen, L., Kaschani, F., Leodolter, J., et al. (2023) · Cell · doi:10.1016/j.cell.2023.04.009 · Cited by 78
Effect of substituents on diarylmethanes for antitubercular activity
Panda, G., Parai, M. K., Das, S. K., et al. (2006) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2006.09.020 · Cited by 75
Yang, J. S., Kim, K. J., Choi, H., et al. (2018) · Annals of Laboratory Medicine · doi:10.3343/alm.2018.38.6.563 · Cited by 75
Bekker, O. B., Sokolov, D. N., Luzina, O. A., et al. (2015) · Medicinal Chemistry Research · doi:10.1007/s00044-015-1348-2 · Cited by 74
“tuberculosis, as on the sensitive strain H37Rv, as well as on MDR strains, with cytotoxicity assay on macrophages (Andries et al., 2005).”
MethodChaudhari, K., Surana, S. J., Jain, P., & Patel, H. (2016) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2016.08.034 · Cited by 75
Strategies in anti-Mycobacterium tuberculosis drug discovery based on phenotypic screening
Grzelak, E. M., Choules, M. P., Gao, W., et al. (2019) · The Journal of Antibiotics · doi:10.1038/s41429-019-0205-9 · Cited by 74
The War against Tuberculosis: A Review of Natural Compounds and Their Derivatives
Maiolini, M., Gause, S., Taylor, J., Steakin, T., Shipp, G. M., Lamichhane, P., Deshmukh, B., Shinde, V. M., Bishayee, A., & Deshmukh, R. R. (2020) · Molecules · doi:10.3390/molecules25133011 · Cited by 78
“The disruption of energy production results in ATP depletion and imbalance in pH homeostasis, resulting in cell death [46].”
BackgroundTimm, J., Bates, M., Solanki, P., et al. (2023) · PLOS Global Public Health · doi:10.1371/journal.pgph.0002283 · Cited by 73
“It binds to subunit C of the mycobacterial ATP synthase, blocking energy production [11].”
BackgroundBiomarkers of treatment response in clinical trials of novel antituberculosis agents
Perrin, F., Lipman, M. C. I., McHugh, T. D., et al. (2007) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(07)70112-3 · Cited by 73
Shortened treatment regimens versus the standard regimen for drug-sensitive pulmonary tuberculosis
Angeline Grace, G., Mittal, A., Jain, S., Tripathy, J. P., Satyanarayana, S., Tharyan, P., & Kirubakaran, R. (2019) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd012918.pub2 · Cited by 72
Is Mycobacterium tuberculosis stressed out? A critical assessment of the genetic evidence
Stallings, C. L., & Glickman, M. S. (2010) · Microbes and Infection · doi:10.1016/j.micinf.2010.07.014 · Cited by 73
Wallis, R. S., Jakubiec, W., Mitton‐Fry, M. J., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030479 · Cited by 72
“This compound, which acts by selective inhibition of mycobacterial ATP synthetase [13], has a delayed time to onset in vivo and in vitro that presumably reflects the size of the ATP pool at the start of drug exposure and the net balance between ATP consumption and production.”
BackgroundIFN- γ Therapy of Tuberculosis and Related Infections
Reljić, R. (2007) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2006.0103 · Cited by 72
Advances in the Treatment of Tuberculosis
Zhang, Y. (2007) · Clinical Pharmacology & Therapeutics · doi:10.1038/sj.clpt.6100362 · Cited by 72
Validation of CoaBC as a Bactericidal Target in the Coenzyme A Pathway of Mycobacterium tuberculosis
Evans, J. C., Trujillo, C., Wang, Z., Eoh, H., Ehrt, S., Schnappinger, D., Boshoff, H. I., Rhee, K. Y., Barry, C. E., & Mizrahi, V. (2016) · ACS Infectious Diseases · doi:10.1021/acsinfecdis.6b00150 · Cited by 73
Torfs, E., Piller, T., Cos, P., & Cappoen, D. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20122868 · Cited by 72
Zhang, L., Zheng, L., Guo, B., et al. (2014) · The Journal of Organic Chemistry · doi:10.1021/jo502192b · Cited by 71
Diacon, A. H., Maritz, J. S., Venter, A., et al. (2010) · European Journal of Clinical Microbiology & Infectious Diseases · doi:10.1007/s10096-010-1043-7 · Cited by 71
“While the ranking of agents and different dosages of TMC207 was similar, the highest dose of TMC207 showed markedly better activity when measured by the TTD than CFU counting when compared to the activity of isoniazid.”
MethodInfluentialSelf-citationThe Future for Early-Stage Tuberculosis Drug Discovery
Zuniga, E. S., Early, J. V., & Parish, T. (2015) · Future Microbiology · doi:10.2217/fmb.14.125 · Cited by 71
Biuković, G., Basak, S., Manimekalai, M. S. S., Rishikesan, S., Roessle, M. W., Dick, T., Rao, S. P. S., Hunke, C., & Grüber, G. (2012) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01039-12 · Cited by 73
“The diarylquinoline TMC207 represents the first pharmacological proof that mycobacterial ATP synthesis can be a target of intervention (8).”
BackgroundSelection of Resistance to Clarithromycin in Mycobacterium abscessus Subspecies
Mougari, F., Bouziane, F., Crockett, F., Nessar, R., Chau, F., Véziris, N., Sapriel, G., Raskine, L., & Cambau, E. (2016) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00943-16 · Cited by 70
Self-citationFacilely accessible quinoline derivatives as potent antibacterial agents
Teng, P., Li, C., Peng, Z., Marie, V. A., Nimmagadda, A., Su, M., Li, Y., Sun, X., & Cai, J. (2018) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2018.05.031 · Cited by 70
The Contribution of Mechanistic Understanding to Phenotypic Screening for First-in-Class Medicines
Swinney, D. C. (2013) · SLAS DISCOVERY · doi:10.1177/1087057113501199 · Cited by 68
“A whole-cell assay was preferred because of its ability to concurrently assess multiple targets.(33) They subsequently used resistance mutations to identify adenosine triphosphate (ATP) synthase as the site of action.”
BackgroundMethodTranslational Research for Tuberculosis Elimination: Priorities, Challenges, and Actions
Lienhardt, C., Lönnroth, K., Menzies, D., Balasegaram, M., Chakaya, J. M., Cobelens, F. G. J., Cohn, J., Denkinger, C. M., Evans, T. G., Källenius, G., et al. (2016) · PLoS Medicine · doi:10.1371/journal.pmed.1001965 · Cited by 70
“Two new drugs—bedaquiline, a diarylquinoline [15], and delamanid, a nitro-imidazole [16]— have been approved by stringent regulatory authorities (including the US Food and Drug”
BackgroundIdentification and validation of novel drug targets in Mycobacterium tuberculosis
Singh, V., & Mizrahi, V. (2016) · Drug Discovery Today · doi:10.1016/j.drudis.2016.09.010 · Cited by 75
Drugging the Folate Pathway in Mycobacterium tuberculosis: The Role of Multi-targeting Agents
Hajian, B., Scocchera, E. W., Shoen, C. M., et al. (2019) · Cell chemical biology · doi:10.1016/j.chembiol.2019.02.013 · Cited by 70
“This is similar to the rate reported for isoniazid, streptomycin, and bedaquiline (Andries et al., 2005; Huitric et al., 2010).”
ResultTMC207 Becomes Bedaquiline, A New Anti-TB Drug
Palomino, J. C., & Martin, A. (2013) · Future Microbiology · doi:10.2217/fmb.13.85 · Cited by 72
Zhang, T., Li, S., Williams, K. N., et al. (2011) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201103-0397oc · Cited by 70
“Doses for the 1/7 regimen were as follows: INH (50) and RPT (15) (9, 23).”
MethodSelf-citationATP Synthase: A Molecular Therapeutic Drug Target for Antimicrobial and Antitumor Peptides
Ahmad, Z., Okafor, F., Azim, S., & Laughlin, T. F. (2013) · Current Medicinal Chemistry · doi:10.2174/0929867311320150003 · Cited by 70
“Another instructive example is the case of Mycobacterium tuberculosis ATP synthase, where two mutations in its c-subunit (D32V and A63P) confer resistance to the tuberculosis drug diarylquinoline [94, 95], providing insight into the causes of drug resistance against tuberculosis.”
BackgroundTHPP target assignment reveals EchA6 as an essential fatty acid shuttle in mycobacteria
Cox, J. A. G., Abrahams, K. A., Alemparte, C., Ghidelli, S., Rullás, J., Angulo‐Barturen, Í., Singh, A., Gurcha, S. S., Nataraj, V., Bethell, S., et al. (2016) · Nature Microbiology · doi:10.1038/nmicrobiol.2015.6 · Cited by 68
Huh, H. J., Kim, S., Jhun, B. W., Shin, S. J., & Koh, W. (2018) · Infection Genetics and Evolution · doi:10.1016/j.meegid.2018.10.003 · Cited by 69
Zhu, S., Shi, K., Zhu, H., et al. (2020) · Organic Letters · doi:10.1021/acs.orglett.0c00085 · Cited by 70
Véziris, N., Ibrahim, M., Lounis, N., et al. (2008) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200711-1736oc · Cited by 70
Self-citationDheda, K. U. J., Cox, H. S., Esmail, A., Wasserman, S. A., Chang, K. C., & Lange, C. G. (2017) · Respirology · doi:10.1111/resp.13143 · Cited by 71
Jiang, M., Yuan, Y. C., Wang, T., et al. (2019) · Chemical Communications · doi:10.1039/c9cc07777d · Cited by 69
Aspergillus fumigatusmetabolism: Clues to mechanisms ofin vivofungal growth and virulence
Willger, S. D., Grahl, N., Willger, S. D., Grahl, N., & Cramer, R. A. (2009) · Medical Mycology · doi:10.1080/13693780802455313 · Cited by 68
“tuberculosis and ATP synthesis suggest that uncovering similar mechanisms in fungal pathogens may also yield new antifungal drugs [58-60].”
BackgroundShowalter, H. D., & Denny, W. A. (2008) · Tuberculosis · doi:10.1016/s1472-9792(08)70032-5 · Cited by 68
New Drugs for the Treatment of Tuberculosis
Ignatius, E. H., & Dooley, K. E. (2019) · Clinics in Chest Medicine · doi:10.1016/j.ccm.2019.08.001 · Cited by 67
Ismail, N. A., Rivière, E., Limberis, J. D., Huo, S., Metcalfe, J. Z., Warren, R. M., & Rie, A. V. (2021) · The Lancet Microbe · doi:10.1016/s2666-5247(21)00175-0 · Cited by 63
Cuyckens, F., Balcaen, L. I. L., Wolf, K. D., et al. (2008) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-007-1761-6 · Cited by 68
Zheng, J. M., Li, Z., Huang, L., et al. (2016) · Organic Letters · doi:10.1021/acs.orglett.6b01008 · Cited by 67
Isoniazid Bactericidal Activity Involves Electron Transport Chain Perturbation
Zeng, S., Soetaert, K., Ravon, F., Vandeput, M., Bald, D., Kauffmann, J., Mathys, V., Wattiez, R., & Fontaine, V. (2019) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01841-18 · Cited by 68
Sarathy, J. P., Ragunathan, P., Shin, J. S., Cooper, C. B., Upton, A. M., Grüber, G., & Dick, T. (2019) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01191-19 · Cited by 69
“(anti-TB) drug that functions by inhibiting mycobacterial F-ATP synthase (7).”
Dookie, N., Khan, A., Padayatchi, N., & Naidoo, K. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.775030 · Cited by 72
Pieroni, M., Wan, B., Cho, S., Franzblau, S. G., & Costantino, G. (2013) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2013.11.007 · Cited by 66
Vilchèze, C., Baughn, A. D., Tufariello, J. M., Leung, L. W., Kuo, M. R., Basler, C. F., Alland, D., Sacchettini, J. C., Freundlich, J. S., & Jacobs, W. R. (2011) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00266-11 · Cited by 69
“The novel TB drugs currently in clinical trials were not discovered through target-based cell screening but through either whole-cell phenotypic screening (TMC207 [1]) or chemical modification of previous hits (PA-824 [35], SQ109 [12], and OPC-67683 [28]).”
BackgroundChallenges and Opportunities in Developing Novel Drugs for TB
Kaneko, T., Cooper, C. B., & Mdluli, K. E. (2011) · Future Medicinal Chemistry · doi:10.4155/fmc.11.115 · Cited by 66
Harbut, M. B., Yang, B., Liu, R., Yano, T., Vilchèze, C., Cheng, B., Lockner, J. W., Guo, H., Yu, C., Franzblau, S. G., et al. (2018) · Angewandte Chemie International Edition · doi:10.1002/anie.201800260 · Cited by 64
Development of Macozinone for TB treatment: An Update
Makarov, V., & Mikušová, K. (2020) · Applied Sciences · doi:10.3390/app10072269 · Cited by 67
“These are bedaquiline [5], delamanid [6] and pretomanid [7], which are currently undergoing several clinical trials aimed at treatment of the drug-resistant TB, as well as at shortening standard TB treatment [8].”
BackgroundMetabolic Versatility of Mycobacterium tuberculosis during Infection and Dormancy
Chang, D. P. S., & Guan, X. L. (2021) · Metabolites · doi:10.3390/metabo11020088 · Cited by 70
Gómez, P. J., Perdigão, J., Gomes, P., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-98862-4 · Cited by 66
Schurig-Briccio, L. A., Yano, T., Rubin, H. N., & Gennis, R. B. (2014) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2014.03.017 · Cited by 70
Warrier, T., Tropis, M., Werngren, J., Diehl, A., Gengenbacher, M., Schlegel, B., Schade, M., Oschkinat, H., Daffé, M., Hoffner, S., et al. (2012) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.05742-11 · Cited by 68
“Several front-runners in current clinical and preclinical studies, such as TMC-207, PA-824, and benzothiazinones, have a novel mode of action (3, 24, 46).”
BackgroundSelf-citationThe Mycobacterium tuberculosis MEP (2C-methyl-d-erythritol 4-phosphate) pathway as a new drug target
Eoh, H., Brennan, P. J., & Crick, D. C. (2008) · Tuberculosis · doi:10.1016/j.tube.2008.07.004 · Cited by 68
Ghajavand, H., Kamakoli, M. K., Khanipour, S., et al. (2019) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.02530-18 · Cited by 66
Empirical ways to identify novel Bedaquiline resistance mutations in AtpE
Karmakar, M., Rodrigues, C. H. M., Holt, K. E., Dunstan, S. J., Denholm, J. T., & Ascher, D. B. (2019) · PLoS ONE · doi:10.1371/journal.pone.0217169 · Cited by 72
“We identified 9 previously published bedaquiline resistant non-synonymous single nucleotide variants (nsSNVs) from in-vitro selection experiments [4, 13, 24, 26].”
BackgroundMethodGrant, S. S., Wellington, S., Kawate, T., et al. (2016) · Cell chemical biology · doi:10.1016/j.chembiol.2016.05.011 · Cited by 65
“2 Cell Chemical Biology 23, 1–12, June 23, 2016 by generating resistant mutants followed by whole-genome sequencing (Andries et al., 2005; Grzegorzewicz et al., 2012; Loerger et al., 2010 Makarov et al., 2009; Stanley et al., 2012).”
BackgroundSquaric acid analogues in medicinal chemistry
Chasák, J., Šlachtová, V., Urban, M., & Brulíková, L. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112872 · Cited by 72
Yang, Q., Pan, G., Wei, J., Wang, W., Tang, Y., & Cai, Y. (2021) · ACS Sustainable Chemistry & Engineering · doi:10.1021/acssuschemeng.0c08771 · Cited by 65
Svensson, E. M., Dooley, K. E., & Karlsson, M. O. (2014) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.03246-14 · Cited by 66
Overview: methods and applications for droplet compartmentalization of biology
Leamon, J. H., Link, D. R., Egholm, M., et al. (2006) · Nature Methods · doi:10.1038/nmeth0706-541 · Cited by 65
Mogi, T., Murase, Y., Mori, M., Shiomi, K., Ōmura, S., Paranagama, M. P., & Kita, K. (2009) · The Journal of Biochemistry · doi:10.1093/jb/mvp096 · Cited by 67
Geng, X., Wu, X., Zhao, P., et al. (2017) · Organic Letters · doi:10.1021/acs.orglett.7b01686 · Cited by 65
Mohassab, A. M., Hassan, H. A., Abdelhamid, D. S., et al. (2017) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2017.09.018 · Cited by 65
Liu, Y., Hu, Y., Cao, Z., et al. (2018) · Advanced Synthesis & Catalysis · doi:10.1002/adsc.201800373 · Cited by 65
Unpacking the Pathogen Box—An Open Source Tool for Fighting Neglected Tropical Disease
Veale, C. G. L. (2019) · ChemMedChem · doi:10.1002/cmdc.201800755 · Cited by 61
Advani, J., Verma, R., Chatterjee, O., Pachouri, P. K., Upadhyay, P., Singh, R. K., Yadav, J., Naaz, F., Ravikumar, R., Buggi, S., et al. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.00309 · Cited by 66
Promiscuous Targets for Antitubercular Drug Discovery: The Paradigm of DprE1 and MmpL3
Degiacomi, G., Belardinelli, J. M., Pasca, M. R., Rossi, E. D., Riccardi, G., & Chiarelli, L. R. (2020) · Applied Sciences · doi:10.3390/app10020623 · Cited by 64
“Indeed, the first new TB drug, Bedaquiline, approved by the Food and Drug Administration (FDA) since 1971, was discovered in a whole-cell HTS campaign [6], and the same origin had both Delamanid [7] and Pretomanid [8], other two drugs recently approved for multidrug resistant tuberculosis (MDR-TB) and extensively drug…”
BackgroundPontali, E., D’Ambrosio, L., Centis, R., Sotgiu, G., & Migliori, G. B. (2017) · European Respiratory Journal · doi:10.1183/13993003.00146-2017 · Cited by 63
Cai, S., Zeng, J., Bai, Y., et al. (2011) · The Journal of Organic Chemistry · doi:10.1021/jo202281x · Cited by 64
Moodley, S., Koorbanally, N. A., Moodley, T., et al. (2014) · Journal of Microbiological Methods · doi:10.1016/j.mimet.2014.06.014 · Cited by 64
Pieroni, M., Tipparaju, S. K., Lun, S., Song, Y., Sturm, A. W., Bishai, W. R., & Kozikowski, A. P. (2011) · ChemMedChem · doi:10.1002/cmdc.201000490 · Cited by 65
Dhillon, J., Andries, K., Phillips, P. P. J., & Mitchison, D. A. (2010) · Tuberculosis · doi:10.1016/j.tube.2010.07.004 · Cited by 63
“The speed with which death occurs therefore depends on two processes (1) the speed with which the ATP synthase is inhibited presumably best measured by the static concentration, which is a type of MIC, and (2) the size of the energy pool at the start of the TMC207 exposure.”
BackgroundSelf-citationSterilizing Activity of Second-Line Regimens Containing TMC207 in a Murine Model of Tuberculosis
Véziris, N., Ibrahim, M., Lounis, N., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0017556 · Cited by 64
“TMC207 has been shown to improve both the bactericidal and the sterilizing activity of the first line regimen RHZ [6,29].”
BackgroundInfluentialSelf-citationBioenergetics of Mycobacterium: An Emerging Landscape for Drug Discovery
Iqbal, I., Bajeli, S., Akela, A. K., & Kumar, A. (2018) · Pathogens · doi:10.3390/pathogens7010024 · Cited by 66
“However, it was only in 2004 [152,153], that an ATP synthase-targeting lead compound of the diarylquinoline class (R207910) was shown to have potent antimycobacterial activity.”
BackgroundMethodInfluentialMarimani, M. D., Ahmad, A., & Duse, A. G. (2018) · Tuberculosis · doi:10.1016/j.tube.2018.10.009 · Cited by 64
“Consequently, mutation in the atpE gene which codes for the F0 subunit of ATP synthase has been confirmed to be responsible for bedaquiline resistance [114].”
BackgroundGenome-Wide Transcriptional Responses of Mycobacterium to Antibiotics
Briffotaux, J., Liu, S., & Gicquel, B. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.00249 · Cited by 62
“Bedaquiline is a new drug approved for the treatment of MDR-TB since 2012, with the ability to inhibit mycobacterial F1F0 ATP synthase (Andries et al., 2005).”
BackgroundAntibiotic research in the age of omics: from expression profiles to interspecies communication
Wecke, T., & Mascher, T. (2011) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkr373 · Cited by 62
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
