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
0 of 14 cited sources checked · 0 supported · 0 flagged
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.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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.
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA 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.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe 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.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA 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.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe 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.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes? Based: unclear
- 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.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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.
Strength:plain· not yet calibratedSingle caseTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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.
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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.
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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.
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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.
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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.
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes? Based: unclearIt 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.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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.
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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.
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably 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.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes? Based: unclearIt 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.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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.
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✗ Checkable: fails✗ Load-bearing: fails✓ Based: passesProbably 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.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Flagged first, then by citations
Cited by
Sorted by citations
Items 701–800 of 2,159
Hartman, H. B., Fell, D. A., Rossell, S., et al. (2014) · Microbiology · doi:10.1099/mic.0.076091-0 · Cited by 43
“…have been developed that specifically inhibit mycobacterial homologues of type II NADH dehydrogenase (phenothiazines and analogous compounds) (Weinstein et al., 2005) and ATP synthase (diarylquinolines) (Andries et al., 2005), indicating the feasibility of targeting a conserved metabolic pathway.”
BackgroundNew treatment options for multidrug-resistant tuberculosis
Field, S. K., Fisher, D., Jarand, J. M., & Cowie, R. L. (2012) · Therapeutic Advances in Respiratory Disease · doi:10.1177/1753465812452193 · Cited by 45
“…active diarylquinoline and the first to undergo clinical testing, TMC207, previously referred to as R207910, is active against both DS- and DR-TB, including strains that are resistant to streptomycin, Z, E, and moxifloxacin [Andries et al. 2005; Lienhardt et al. 2010; van den Boogard et al. 2009].”
BackgroundInfluentialAntimicrobial Properties of Various Psychotropic Drugs Against Broad Range Microorganisms
Kalaycı, S., Demirci, S., & Şahi̇n, F. (2015) · Current Psychopharmacologye · doi:10.2174/2211556004666150520230121 · Cited by 43
Kaniga, K., Aono, A., Borroni, E., et al. (2020) · Journal of Clinical Microbiology · doi:10.1128/jcm.01677-19 · Cited by 43
“Bedaquiline (BDQ) is a diarylquinoline antimycobacterial agent that acts differently from other anti-TB agents through inhibiting ATP synthase, leading to ATP depletion and decreased mycobacterial survival; it also has bactericidal and sterilizing properties (3).”
BackgroundRational Design and Synthesis of Thioridazine Analogues as Enhancers of the Antituberculosis Therapy
Pieroni, M., Machado, D., Azzali, E., Costa, S. S., Couto, I., Costantino, G., & Viveiros, M. (2015) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b00428 · Cited by 44
MurF Inhibitors with Antibacterial Activity: Effect on Muropeptide Levels
Baum, E. Z., Crespo‐Carbone, S. M., Foleno, B. D., Simon, L. D., Guillemont, J., Macielag, M. J., & Bush, K. (2009) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00166-09 · Cited by 45
“We note that the MurF inhibitors DQ1 and DQ2 belong to the same chemical class as the diarylquinoline ATP synthase inhibitor TMC207 (R207910), an anti-tuberculosis compound (2, 21); however, the DQ compounds in E.”
BackgroundSelf-citationWlodarska, M., Johnston, J. C., Gardy, J. L., & Tang, P. (2015) · Clinical Microbiology Reviews · doi:10.1128/cmr.00124-14 · Cited by 42
“smegmatis isolates before and after treatment with the investigational compound R207910 (now called bedaquiline) (44).”
BackgroundA Preclinical Candidate Targeting Mycobacterium tuberculosis KasA
Inoyama, D., Awasthi, D., Capodagli, G. C., Tsotetsi, K., Sukheja, P., Zimmerman, M. D., Li, S.-G., Jadhav, R. D., Russo, R., Wang, X., et al. (2020) · Cell chemical biology · doi:10.1016/j.chembiol.2020.02.007 · Cited by 41
“The frequency of resistance compares favorably with that for the tuberculosis drug bedaquiline (10‒7–10‒8) (Andries et al., 2005).”
BackgroundTrehalose Recycling Promotes Energy-Efficient Biosynthesis of the Mycobacterial Cell Envelope
Pohane, A. A., Carr, C. R., Garhyan, J., Swarts, B. M., & Siegrist, M. S. (2021) · mBio · doi:10.1128/mbio.02801-20 · Cited by 40
Courbon, G. M., Palme, P. R., Mann, L., Richter, A., Imming, P., & Rubinstein, J. L. (2023) · The EMBO Journal · doi:10.15252/embj.2023113687 · Cited by 46
“This uncoupling property of BDQ has been observed in vitro at micromolar concentrations and was proposed to be important for the drug’s ability to kill mycobacteria in vivo (Andries et al, 2005; Hards et al, 2015).”
BackgroundInfluentialDunn, E. A., Roxburgh, M., Larsen, L., Smith, R. A. J., McLellan, A. D., Heikal, A., Murphy, M. P., & Cook, G. M. (2014) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2014.07.050 · Cited by 46
After 40 years, new medicine for combating TB
Mirsaeidi, M. S. (2013) · International Journal of Mycobacteriology · doi:10.1016/j.ijmyco.2013.01.004 · Cited by 42
Kamal, Ä., Azeeza, S., Malik, M. S., Shaik, A. A., & Rao, M. V. (2008) · Journal of Pharmacy & Pharmaceutical Sciences · doi:10.18433/j36k5k · Cited by 42
Cholesterol metabolism: a potential therapeutic target in Mycobacteria
Abuhammad, A. (2016) · British Journal of Pharmacology · doi:10.1111/bph.13694 · Cited by 42
“These efforts culminated in the approval of two new drugs for the treatment of MDR-TB as part of a combination regimen: the ATP synthase inhibitor bedaquiline (Andries et al., 2005; Cohen, 2013; Pym et al., 2015) and delamanid (Blair and Scott, 2015; Gupta et al., 2015; WHO, 2015).”
BackgroundA Therapeutic Connection between Dietary Phytochemicals and ATP Synthase
Ahmad, Z., Hassan, S. S., & Azim, S. (2017) · Current Medicinal Chemistry · doi:10.2174/0929867324666170823125330 · Cited by 42
“Administration in 2012, is highly selective in its inhibition of the Fo sector of ATP synthase in mycobacterial species [2, 57-61].”
BackgroundLi, B., Ye, M., Guo, Q., Zhang, Z., Yang, S., Ma, W., Yu, F., & Chu, H. (2018) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00175-18 · Cited by 44
“6 mg/liter at standard oral doses (18), and it can be extensively distributed to tissues, including the lungs, according to the pharmacokinetic studies (19).”
Wang, Y., Chen, C., Peng, J., et al. (2013) · Angewandte Chemie · doi:10.1002/ange.201300586 · Cited by 42
Novel Links between Antibiotic Resistance and Antibiotic Production
Nodwell, J. R. (2007) · Journal of Bacteriology · doi:10.1128/jb.00356-07 · Cited by 43
The potential impact of structural genomics on tuberculosis drug discovery
Arcus, V. L., Lott, J. S., Johnston, J. M., & Baker, E. N. (2006) · Drug Discovery Today · doi:10.1016/s1359-6446(05)03667-6 · Cited by 42
Upadhayaya, R. S., Shinde, P. D., Sayyed, A. Y., et al. (2010) · Organic & Biomolecular Chemistry · doi:10.1039/c0ob00445f · Cited by 42
Pharmacokinetics and pharmacodynamics in the development of anti-tuberculosis drugs
Davies, G., & Nuermberger, E. L. (2008) · Tuberculosis · doi:10.1016/s1472-9792(08)70037-4 · Cited by 44
Berube, B. J., & Parish, T. (2017) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01677-17 · Cited by 44
Inhibitors of ATP Synthase as New Antibacterial Candidates
Mackieh, R., Al-Bakkar, N., Kfoury, M., et al. (2023) · Antibiotics · doi:10.3390/antibiotics12040650 · Cited by 41
“coli, Helicobacter pylori, and Haemophilus influenzae [48].”
BackgroundFluoroquinolones for treating tuberculosis (presumed drug-sensitive)
Ziganshina, L. E., Титаренко, А. Ф., & Davies, G. (2013) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd004795.pub4 · Cited by 41
Yempalla, K. R., Munagala, G., Singh, S., et al. (2015) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.5b00141 · Cited by 41
Ekins, S., Freundlich, J. S., & Reynolds, R. C. (2014) · Journal of Chemical Information and Modeling · doi:10.1021/ci500264r · Cited by 41
Gene Transfer in Mycobacterium tuberculosis : Shuttle Phasmids to Enlightenment
Jacobs, W. R. (2014) · Microbiology Spectrum · doi:10.1128/microbiolspec.mgm2-0037-2013 · Cited by 42
“smegmatis mc(2)155, which was subsequently used to identify and validate the target (28).”
MethodLi, X., Liu, N., Zhang, H., Knudson, S. E., Li, H., Lai, C., Simmerling, C. L., Slayden, R. A., & Tonge, P. J. (2011) · ACS Medicinal Chemistry Letters · doi:10.1021/ml200141e · Cited by 41
Recent advances in antituberculous drug development and novel drug targets
Tomioka, H., Tatano, Y., Yasumoto, K., & Shimizu, T. (2008) · Expert Review of Respiratory Medicine · doi:10.1586/17476348.2.4.455 · Cited by 40
The Anti-Tuberculosis Agents Under Development and the Challenges Ahead
Kumar, D., Negi, B., & Rawat, D. S. (2015) · Future Medicinal Chemistry · doi:10.4155/fmc.15.128 · Cited by 42
Challenges of TB and HIV co-treatment
Tornheim, J. A., & Dooley, K. E. (2018) · Current Opinion in HIV and AIDS · doi:10.1097/coh.0000000000000495 · Cited by 41
A safety evaluation of bedaquiline for the treatment of multi-drug resistant tuberculosis
Cohen, K., & Maartens, G. (2019) · Expert Opinion on Drug Safety · doi:10.1080/14740338.2019.1648429 · Cited by 41
Elucidating the Mechanisms of Action of Antimicrobial Agents
HUDSON, M. A., & Lockless, S. W. (2022) · mBio · doi:10.1128/mbio.02240-21 · Cited by 42
Solution Structure and Dynamics of Peptidyl-tRNA Hydrolase from Mycobacterium tuberculosis H37Rv
Pulavarti, S. V. S. R. K., Jain, A., Pathak, P. P., Mahmood, A., & Arora, A. (2008) · Journal of Molecular Biology · doi:10.1016/j.jmb.2008.02.027 · Cited by 39
Ahmad, Z., Ahmad, M., Okafor, F., Jones, J., Abunameh, A., Cheniya, R. P., & Kady, I. O. (2012) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2012.01.019 · Cited by 41
A review of tuberculosis: Focus on bedaquiline
Chan, B., Khadem, T. M., & Brown, J. E. (2013) · American Journal of Health-System Pharmacy · doi:10.2146/ajhp130199 · Cited by 41
Thymoquinone Inhibits Escherichia coli ATP Synthase and Cell Growth
Ahmad, Z., Laughlin, T. F., & Kady, I. O. (2015) · PLoS ONE · doi:10.1371/journal.pone.0127802 · Cited by 41
“Blocking the synthesis of ATP by targeting subunit c of ATP synthase is being used to treat tuberculosis [12].”
Method4Tuberculosis Chemotherapy: Recent Developments and Future Perspectives
Bhowruth, V., Dover, L. G., & Besra, G. S. (2007) · Progress in medicinal chemistry · doi:10.1016/s0079-6468(06)45504-1 · Cited by 40
Andrés, M. T., Acosta-Zaldívar, M., & Fierro, J. F. (2016) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.03130-15 · Cited by 41
“For example, bedaquiline, which belongs to the diarylquinoline class of drugs and efficiently inhibits the H -ATPase (F-type ATPase) of Mycobacterium tuberculosis, has been approved for treatment of multidrug-resistant tuberculosis (21).”
BackgroundYanofsky, D. J., Trani, J. M. D., Król, S. K., Abdelaziz, R., Bueler, S. A., Imming, P., Brzezinski, P., & Rubinstein, J. L. (2021) · eLife · doi:10.7554/elife.71959 · Cited by 40
Keller, P. M., Hömke, R., Ritter, C., et al. (2015) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00614-15 · Cited by 40
“Thus, resistance may develop independently of treatment with bedaquiline (2, 7).”
BackgroundMethodResultInfluentialDesign, synthesis and antimycobacterial activity evaluation of natural oridonin derivatives
Xu, S., Li, D., Pei, L., Yao, H., Wang, C., Cai, H., Yao, H., Wu, X., & Xu, J. (2014) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2014.04.119 · Cited by 40
Moir, D. T., Opperman, T. J., Butler, M. M., & Bowlin, T. L. (2012) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2012.07.004 · Cited by 40
The Talking Mycobacterium abscessus Blues
Griffith, D. E. (2011) · Clinical Infectious Diseases · doi:10.1093/cid/ciq252 · Cited by 40
Tuberculosis Drugs: New Candidates and How to Find More
Sala, C., & Hartkoorn, R. C. (2011) · Future Microbiology · doi:10.2217/fmb.11.46 · Cited by 42
Biological evaluation of novel substituted chloroquinolines targeting mycobacterial ATP synthase
Khan, S. R., Singh, S., Roy, K. K., Akhtar, M. S., Saxena, A. K., & Krishnan, M. Y. (2012) · International Journal of Antimicrobial Agents · doi:10.1016/j.ijantimicag.2012.09.012 · Cited by 41
Winglee, K., Manson, A. L., Maïga, M., Abeel, T., Shea, T., Desjardins, C. A., Diarra, B., Baya, B., Sanogo, M., Diallo, S., et al. (2016) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0004332 · Cited by 39
A Cinchona Alkaloid Antibiotic That Appears To Target ATP Synthase in Streptococcus pneumoniae
Wang, X., Zeng, Y., Li, S., Larson, P. G., Liu, X., Zou, X., Wang, S., Guo, K., Ma, C., Zhang, G., et al. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b01353 · Cited by 40
Kalia, N. P., Lee, B. S., Rahman, N. B. A., Moraski, G. C., Miller, M. J., & Pethe, K. (2019) · Scientific Reports · doi:10.1038/s41598-019-44887-9 · Cited by 42
Kaushik, A., Ammerman, N. C., Tyagi, S. K., Saini, V., Vervoort, I., Lachau‐Durand, S., Nuermberger, E. L., & Andries, K. (2019) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00007-19 · Cited by 39
“The daily bedaquiline dose of 25 mg/kg represents the 317 standard dose used in TB treatment studies in mice (22, 28).”
BackgroundMethodSelf-citationKidwai, S., Bouzeyen, R., Chakraborti, S., Khare, N., Das, S., Gosain, T. P., Behura, A., Meena, C. L., Dhiman, R., Essafi, M., et al. (2019) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00996-19 · Cited by 40
Alternative and Experimental Therapies of Mycobacterium abscessus Infections
Meir, M., & Barkan, D. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21186793 · Cited by 40
“In Mycobacterium tuberculosis, it was shown to act through inhibition of the ATP Synthase [48], which is considered true in other mycobacteria as well.”
BackgroundAlcaraz, M., Sharma, B., Roquet, F., Condé, C., Cochard, T., Biet, F., Kumar, V., & Kremer, L. (2022) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2022.114531 · Cited by 42
Nakano, C., & Hoshino, T. (2009) · ChemBioChem · doi:10.1002/cbic.200900248 · Cited by 40
Prevention of Drug Carryover Effects in Studies Assessing Antimycobacterial Efficacy of TMC207
Lounis, N., Gevers, T., Berg, J. V. D., et al. (2008) · Journal of Clinical Microbiology · doi:10.1128/jcm.00177-08 · Cited by 40
Self-citationMechanisms of Pyrazinamide Action and Resistance
Zhang, Y., Shi, W., Zhang, W., & Mitchison, D. A. (2015) · ASM Press eBooks · doi:10.1128/9781555818845.ch24 · Cited by 40
Contemporary Pharmacotherapies for Nontuberculosis Mycobacterial Infections: A Narrative Review
Johnson, T. M., Byrd, T. F., Drummond, W. K., et al. (2023) · Infectious Diseases and Therapy · doi:10.1007/s40121-022-00750-5 · Cited by 39
“Bedaquiline is a diarylquinoline antibiotic that inhibits the proton pump of mycobacterial ATP synthase, which is conserved across mycobacterial species [33].”
BackgroundEvans, J. C., & Mizrahi, V. (2015) · Frontiers in Microbiology · doi:10.3389/fmicb.2015.00812 · Cited by 38
“…(targeted by imidazopyridines other chemotypes) in energy metabolism, and DprE1 (benzothiazinones and other chemotypes) in arabinan biosynthesis (Andries et al., 2005; Petrella et al., 2006; Makarov et al., 2009; Magnet et al., 2010; Abrahams et al., 2012b; Stanley et al., 2012; Pethe et al.,…”
BackgroundAssessment of the Efficacy of New Anti-Tuberculosis Drugs
Mitchison, D. A., & Davies, G. (2008) · The Open Infectious Diseases Journal · doi:10.2174/1874279300802010059 · Cited by 39
“TMC-207 blocks the mycobacterial ATP synthase and therefore respiration [35].”
BackgroundThe c-Ring of the F1FO-ATP Synthase: Facts and Perspectives
Nesci, S., Trombetti, F., Ventrella, V., & Pagliarani, A. (2015) · The Journal of Membrane Biology · doi:10.1007/s00232-015-9860-3 · Cited by 40
Nguyen, T. V. A., Cao, T. B. T., Akkerman, O. W., et al. (2016) · Expert Review of Clinical Pharmacology · doi:10.1080/17512433.2016.1200462 · Cited by 39
“The half-life is independent of administered dose [2,13,25,26].”
BackgroundInfluentialMomin, M. A. M., Rangnekar, B., Sinha, S., et al. (2019) · Pharmaceutics · doi:10.3390/pharmaceutics11100502 · Cited by 39
Adeniji, A. A., Knoll, K. E., & Loots, D. T. (2020) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-020-10606-y · Cited by 39
“22 μM) (Andries et al. 2005), and its characteristic non-cross-resistance to MDR and XDR-Mtb strains (Kaur et al.”
BackgroundInfluentialF1·Fo ATP Synthase/ATPase: Contemporary View on Unidirectional Catalysis
Zharova, T. V., Grivennikova, V. G., & Borisov, V. B. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24065417 · Cited by 41
“ticular as anti-tuberculosis drugs [14,15], we will also discuss the strategy for developing”
BackgroundBorisov, V. B., Forte, E., Siletsky, S. A., Arese, M., Davletshin, A. I., Sarti, P., & Giuffrè, A. (2015) · Biochemistry (Moscow) · doi:10.1134/s0006297915050077 · Cited by 38
Akula, M., Sridevi, J. P., Yogeeswari, P., Sriram, D., & Bhattacharya, A. (2014) · Monatshefte für Chemie - Chemical Monthly · doi:10.1007/s00706-013-1141-1 · Cited by 39
Koh, J.-J., Zou, H., Mukherjee, D., et al. (2016) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2016.07.068 · Cited by 39
Ramachandran, S. A., Panda, M., Mukherjee, K., Choudhury, N. R., Tantry, S. J., Kedari, C. K., Ramachandran, V., Sharma, S., Ramya, V. K., Guptha, S., et al. (2013) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2013.06.043 · Cited by 38
Mycobacterium tuberculosisP-Type ATPases: Possible Targets for Drug or Vaccine Development
Novoa‐Aponte, L., & Soto, C. Y. (2014) · BioMed Research International · doi:10.1155/2014/296986 · Cited by 38
“In this regard, a mycobacterial F 1 -F 0 ATP synthase inhibitor, such as TMC207 [52], could be used in combination with compounds that mediate Mtb P-type ATPase activation, thus promoting ATP consumption and avoiding ATP synthesis in the pathogen.”
BackgroundMultidrug and extensively drug-resistant tuberculosis
Maitre, T., Aubry, A., Jarlier, V., Robert, J., Véziris, N., Bernard, C., Sougakoff, W., Brossier, F., Cambau, E., Mougari, F., et al. (2017) · Médecine et Maladies Infectieuses · doi:10.1016/j.medmal.2016.07.006 · Cited by 41
Self-citationSellamuthu, S., Singh, M., Kumar, A., & Singh, S. K. (2017) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2017.1327577 · Cited by 39
Ramirez-Busby, S. M., Rodwell, T. C., Fink, L., Catanzaro, D. G., Jackson, R. L., Pettigrove, M. E., Catanzaro, A., & Valafar, F. (2017) · Scientific Reports · doi:10.1038/s41598-017-03452-y · Cited by 36
Deshmukh, A. R., Dhumal, S. T., Nawale, L., et al. (2019) · Synthetic Communications · doi:10.1080/00397911.2018.1564928 · Cited by 38
Qiu, Y., Niu, Y.-J., Wei, X., et al. (2019) · The Journal of Organic Chemistry · doi:10.1021/acs.joc.9b00181 · Cited by 38
Proton-pumping F-ATPase plays an important role in Streptococcus mutans under acidic conditions
Sekiya, M., Izumisawa, S., Iwamoto-Kihara, A., Fan, Y., Shimoyama, Y., Sasaki, M., & Nakanishi‐Matsui, M. (2019) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2019.03.014 · Cited by 38
Berube, B. J., Russell, D., Castro, L., Choi, S., Narayanasamy, P., & Parish, T. (2019) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.02661-18 · Cited by 39
Antitubercular Triazines: Optimization and Intrabacterial Metabolism
Wang, X., Inoyama, D., Russo, R., Li, S.-G., Jadhav, R. D., Stratton, T. P., Mittal, N., Bilotta, J. A., Singleton, E., Kim, T., et al. (2019) · Cell chemical biology · doi:10.1016/j.chembiol.2019.10.010 · Cited by 38
“While bedaquiline inhibits ATP biosynthesis (Andries et al., 2005), delamanid, or OPC-67683, appears to target M.”
BackgroundMulti-Omics Technologies Applied to Tuberculosis Drug Discovery
Goff, A., Cantillon, D. M., Wildner, L. M., & Waddell, S. J. (2020) · Applied Sciences · doi:10.3390/app10134629 · Cited by 38
“ATP synthase anchored in the mycobacterial membrane [30].”
BackgroundTerminal Respiratory Oxidases: A Targetables Vulnerability of Mycobacterial Bioenergetics?
Bajeli, S., Baid, N., Kaur, M., Pawar, G. P., Chaudhari, V. D., & Kumar, A. (2020) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2020.589318 · Cited by 38
Li, M., Patel, H. V., Cognetta, A. B., Smith, T. C., Mallick, I., Cavalier, J., Previti, M. L., Canaan, S., Aldridge, B. B., Cravatt, B. F., et al. (2021) · Cell chemical biology · doi:10.1016/j.chembiol.2021.09.002 · Cited by 37
“Target validation has depended largely on high-throughput genetic methods, such as generating spontaneous mutations (Andries et al., 2005; Christophe et al., 2009; Grzegorzewicz et al., 2012; Makarov et al., 2009; Pethe et al., 2013; Remuiñán et al., 2013; Stanley et al., 2013; Stover et al., 2000) and over- or undere…”
Determination of Bedaquiline in Human Serum Using Liquid Chromatography-Tandem Mass Spectrometry
Alffenaar, J. C., Bolhuis, M. S., van Hateren, K., et al. (2015) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00276-15 · Cited by 38
“Since the antimicrobial action of bedaquiline is exposure dependent (2, 3), it is necessary, as with any drug with exposuredependent killing characteristics, that target exposures are reached.”
BackgroundCombined therapy for tuberculosis and HIV-1: the challenge for drug discovery
Pepper, D. J., Meintjes, G., McIlleron, H., & Wilkinson, R. J. (2007) · Drug Discovery Today · doi:10.1016/j.drudis.2007.08.001 · Cited by 38
Epidemiology and Treatment of Multidrug Resistant Tuberculosis
Mitnick, C. D., Appleton, S. C., & Shin, S. S. (2008) · Seminars in Respiratory and Critical Care Medicine · doi:10.1055/s-0028-1085702 · Cited by 37
Recent Advances in Methodologies for the Discovery of Antimycobacterial Drugs
Primm, T. P., & Franzblau, S. G. (2007) · Current Bioactive Compounds · doi:10.2174/157340707781695550 · Cited by 38
“smegmatis [17].”
Extensively Drug-Resistant Tuberculosis: Are We Learning from History or Repeating It?
HAMILTON, C. D., Sterling, T. R., Blumberg, H. M., et al. (2007) · Clinical Infectious Diseases · doi:10.1086/519292 · Cited by 38
The chemotherapy of leprosy: An interpretive history
GELBER, R. H., & Grosset, J. H. E. (2012) · Leprosy Review · doi:10.47276/lr.83.3.221 · Cited by 38
Antibiotikaresistenzen gezielt überwinden
Chellat, M. F., Raguž, L., & Riedl, R. (2016) · Angewandte Chemie · doi:10.1002/ange.201506818 · Cited by 37
New drugs to treat multidrug-resistant tuberculosis: the case for bedaquiline
Leibert, E. M., Rom, W. N., & DANCKERS, M. (2014) · Therapeutics and Clinical Risk Management · doi:10.2147/tcrm.s37743 · Cited by 37
“Bedaquiline has a large volume of distribution and a half-life of 43–64 hours in plasma and 28–92 hours in tissue (including lung and spleen).(24) Bedaquiline’s long terminal half-life of 4–5 months(31) raises concerns that even after drug cessation, effective monotherapy may continue for months, potentially leading t…”
InfluentialBayesian models for screening and TB Mobile for target inference with Mycobacterium tuberculosis
Ekins, S., Casey, A. C., Roberts, D., Parish, T., & Bunin, B. A. (2013) · Tuberculosis · doi:10.1016/j.tube.2013.12.001 · Cited by 38
New bithiazolyl hydrazones: Novel synthesis, characterization and antitubercular evaluation
Bhalerao, M. B., Dhumal, S. T., Deshmukh, A. R., Nawale, L., Khedkar, V. M., Sarkar, D. M., & Mane, R. A. (2016) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2016.11.056 · Cited by 37
EthA/R-Independent Killing of Mycobacterium tuberculosis by Ethionamide
Ang, M. L. T., Rahim, S. Z. Z., de Sessions, P. F., Lin, W., Koh, V. J. W., Pethe, K., Hibberd, M. L., & Alonso, S. (2017) · Frontiers in Microbiology · doi:10.3389/fmicb.2017.00710 · Cited by 36
Host-directed therapies offer novel opportunities for the fight against tuberculosis
Machelart, A., Song, O., Hoffmann, E., & Brodin, P. M. (2017) · Drug Discovery Today · doi:10.1016/j.drudis.2017.05.005 · Cited by 37
Molecular Diagnostics forMycobacterium tuberculosisInfection
Dicks, K. V., & Stout, J. E. (2018) · Annual Review of Medicine · doi:10.1146/annurev-med-040717-051502 · Cited by 37
A Therapeutic Role for the F1FO-ATP Synthase
Nesci, S., Trombetti, F., Algieri, C., & Pagliarani, A. (2019) · SLAS DISCOVERY · doi:10.1177/2472555219860448 · Cited by 37
Abrahams, K. A., & Besra, G. S. (2020) · RSC Medicinal Chemistry · doi:10.1039/d0md00261e · Cited by 38
Design and synthesis of novel anti-tuberculosis agents from the celecoxib pharmacophore
Salunke, S. B., Azad, A. K., Kapuriya, N. P., et al. (2015) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2015.03.041 · Cited by 37
Chemotherapeutic Interventions Against Tuberculosis
Shakya, N., Garg, G., Agrawal, B., et al. (2012) · Pharmaceuticals · doi:10.3390/ph5070690 · Cited by 37
Combating antimicrobial resistance in malaria, HIV and tuberculosis
Duffey, M., Shafer, R. W., Timm, J., Burrows, J. N., Fotouhi, N., Cockett, M. I., & Leroy, D. (2024) · Nature Reviews Drug Discovery · doi:10.1038/s41573-024-00933-4 · Cited by 40
“For example, early laboratory experiments on bedaquiline indicated that variants in the atpE gene, encoding the drug’s target ATP synthase subunit C, led to high-level resistance 123 .”
Shah, N. B., & Duncan, T. M. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.665059 · Cited by 36
“Mycobacterial ATP synthase is the target of a new class of antibiotics, the diarylquinolines, and the lead drug, bedaquiline, has been approved for treatment of multidrug-resistant tuberculosis (25, 69).”
BackgroundRienksma, R. A., Diez, M. S., Spina, L., Schaap, P. J., & dos Santos, V. A. P. M. (2014) · Seminars in Immunology · doi:10.1016/j.smim.2014.09.013 · Cited by 36
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
