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 601–700 of 2,159
Pediatric Tuberculosis Management: A Global Challenge or Breakthrough?
Maphalle, L. N. F., Michniak‐Kohn, B. B., Ogunrombi, M. O., & Adeleke, O. A. (2022) · Children · doi:10.3390/children9081120 · Cited by 64
“12 mg/mL for drug-resistant strains for both chronic and acute TB [261].”
BackgroundThe evolving biology of Mycobacterium tuberculosis drug resistance
Jones, R. M., Adams, K. N., Eldesouky, H. E., & Sherman, D. R. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.1027394 · Cited by 54
“Bedaquiline (BDQ) mmpR (Rv0678), atpE, pepQ atpB? (suggested) (Andries et al., 2005; de Jonge et al., 2007; Huitric et al., 2010; Andries et al., 2014; Nieto Ramirez et al., 2020)”
Shang, S., Shanley, C. A., Caraway, M. L., et al. (2010) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00978-10 · Cited by 51
“Within the current drug discovery pipeline (12), a particularly attractive new candidate is the diarylquinolone TMC207 (2).”
BackgroundDartois, V. A., & Barry, C. E. (2010) · Current Clinical Pharmacology · doi:10.2174/157488410791110797 · Cited by 50
The early bactericidal activity of antituberculosis drugs
Diacon, A. H., & Donald, P. R. (2014) · Expert Review of Anti-infective Therapy · doi:10.1586/14787210.2014.870884 · Cited by 49
“Although its activity over the 7-day period was inferior to that of INH and RMP, the 400 mg dosage matched their activity during the period days 4–7; this slow onset of BDQ activity was not unexpected based on experience in previous in vitro and in vivo animal studies and subsequent experiments studying the mechanism…”
Resistance in tuberculosis: what do we know and where can we go?
Green, K. D., & Garneau‐Tsodikova, S. (2013) · Frontiers in Microbiology · doi:10.3389/fmicb.2013.00208 · Cited by 52
“A plausible way to attack the non-growing bacilli is to affect their ATP storage by inactivating ATP synthase to deplete the ATP and eventually kill the bacilli (Andries et al., 2005).”
Tuyiringire, N., Tusubira, D., Munyampundu, J.-P., Tolo, C. U., Muvunyi, C. M., & Ogwang, P. E. (2018) · Clinical and Translational Medicine · doi:10.1186/s40169-018-0208-3 · Cited by 52
Zou, L., Zhu, H., Zhu, S., et al. (2019) · The Journal of Organic Chemistry · doi:10.1021/acs.joc.9b01577 · Cited by 51
Tuberculosis drug discovery: Progression and future interventions in the wake of emerging resistance
Perveen, S., Kumari, D., Singh, K., & Sharma, R. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2021.114066 · Cited by 54
Kalia, N. P., Singh, S., Hards, K., Cheung, C., Sviriaeva, E. N., Banaei‐Esfahani, A., Aebersold, R. H., Berney, M., Cook, G. M., & Pethe, K. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112444 · Cited by 47
Trivedi, A. R., Dodiya, D. K., Dholariya, B. H., et al. (2011) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2011.07.068 · Cited by 50
Hatami, H., Sotgiu, G., Bostanghadiri, N., et al. (2022) · Jornal Brasileiro de Pneumologia · doi:10.36416/1806-3756/e20210384 · Cited by 50
New advances in antibiotic development and discovery
Alekshun, M. N. (2005) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.14.2.117 · Cited by 50
Investigating the anti-proliferative activity of styrylazanaphthalenes and azanaphthalenediones
Mrozek‐Wilczkiewicz, A., Kalinowski, D. S., Musioł, R., et al. (2010) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2010.02.025 · Cited by 50
Fármacos con actividad frente a Mycobacterium tuberculosis
Coll, P. (2009) · Enfermedades Infecciosas y Microbiología Clínica · doi:10.1016/j.eimc.2009.06.010 · Cited by 49
Almeida, D., Converse, P. J., Li, S.-Y., et al. (2021) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01412-21 · Cited by 49
“in vitro identified mutations in the atpE gene as the main cause of resistance (13).”
BackgroundWu, S.-H., Xiao, Y.-X., Hsiao, H.-C., & Jou, R. (2022) · Microbiology Spectrum · doi:10.1128/spectrum.02605-22 · Cited by 48
Pai, H., Ndjeka, N. O., Mbuagbaw, L. C. E., Kaniga, K., Birmingham, E., Mao, G., Alquier, L., Davis, K. J., Bodard, A., Williams, A., et al. (2022) · BMC Infectious Diseases · doi:10.1186/s12879-022-07861-x · Cited by 50
Dynamic 18F-Pretomanid PET imaging in animal models of TB meningitis and human studies
Mota, F., Ruiz-Bedoya, C. A., Tucker, E. W., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-35730-3 · Cited by 49
Inhibition of M. tuberculosis and human ATP synthase by BDQ and TBAJ-587
Zhang, Y., Lai, Y., Zhou, S., Ran, T., Zhang, Y., Zhao, Z., Feng, Z., Yu, L., Xu, J., Shi, K., et al. (2024) · Nature · doi:10.1038/s41586-024-07605-8 · Cited by 54
An Overview Of Tuberculosis Chemotherapy – A Literature Review
Sarkar, S., & Suresh, M. R. (2011) · Journal of Pharmacy & Pharmaceutical Sciences · doi:10.18433/j33591 · Cited by 50
“Human studies with this drug have showed good efficacy in MDR-TB, with acceptable toxic effect (31).”
BackgroundTorrea, G., Coeck, N., Desmaretz, C., van de Parre, T. J. L., Poucke, T. V., Lounis, N., de Jong, B. C., & Rigouts, L. (2015) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkv117 · Cited by 49
Self-citationChallenges in the development of drugs for the treatment of tuberculosis
Shehzad, A., Rehman, G., Ul‐Islam, M., Khattak, W. A., & Lee, Y. S. (2013) · The Brazilian Journal of Infectious Diseases · doi:10.1016/j.bjid.2012.10.009 · Cited by 51
Yano, T., Rahimian, M., Aneja, K. K., et al. (2014) · Biochemistry · doi:10.1021/bi4013897 · Cited by 49
He, C., Preiß, L., Wang, B., Fu, L., Wen, H., Zhang, X., Cui, H., Meier, T. W., & Yin, D. (2016) · ChemMedChem · doi:10.1002/cmdc.201600441 · Cited by 50
Dual Mechanism of Action of 5-Nitro-1,10-Phenanthroline against Mycobacterium tuberculosis
Kidwai, S., Park, C.-Y., Mawatwal, S., Tiwari, P., Jung, M. G., Gosain, T. P., Kumar, P., Alland, D., Kumar, S., Bajaj, A., et al. (2017) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00969-17 · Cited by 49
“TMC-207 inhibits the ATP synthase enzyme and is active against both replicating and nonreplicating bacteria (11, 12).”
BackgroundXu, J., Tasneen, R., Peloquin, C. A., et al. (2017) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01692-17 · Cited by 49
“The seemingly discrepant results with different bedaquiline doses may be explained by previous results suggesting that 25 mg/kg bedaquiline approaches the maximally effective dose (9).”
ResultAnti-tubercular agents. Part 3. Benzothiadiazine as a novel scaffold for anti-Mycobacterium activity
Kamal, Ä., Reddy, K. S., Ahmed, S. K., et al. (2005) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2005.08.063 · Cited by 49
Borah, P., Deb, P. K., Venugopala, K. N., Al‐Shar’i, N. A., Singh, V., Deka, S., Srivastava, A., Tiwari, V. K., & Mailavaram, R. P. (2020) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026621999201211200447 · Cited by 49
Cole, S. T., & Alzari, P. M. (2005) · Science · doi:10.1126/science.1108379 · Cited by 48
New Drugs and Treatment Regimens
Sloan, D. J., Davies, G., & Khoo, S. (2013) · Current Respiratory Medicine Reviews · doi:10.2174/1573398x113099990017 · Cited by 48
“Early animal studies indicated the potency of bedaquilinie as monotherapy [60] or in combination with pyrazinamide-rifapentine [64].”
BackgroundGaurrand, S., Desjardins, S., Meyer, C., et al. (2006) · Chemical Biology & Drug Design · doi:10.1111/j.1747-0285.2006.00410.x · Cited by 48
“R207910 was shown to target the subunit c of the F0 complex and block the proton translocation leading to inadequate synthesis of ATP (3).”
BackgroundInfluentialSelf-citationKögler, M., Busson, R. H., Jonghe, S. D., et al. (2012) · Chemistry & Biodiversity · doi:10.1002/cbdv.201100285 · Cited by 48
Zhou, W., & Lei, J. (2014) · Chemical Communications · doi:10.1039/c4cc00939h · Cited by 48
Mycobacterial Pathogenomics and Evolution
Bottai, D., Stinear, T. P., Supply, P., & Brosch, R. (2014) · Microbiology Spectrum · doi:10.1128/microbiolspec.mgm2-0025-2013 · Cited by 55
“Information on the genome content and “ omic ” approaches in general are helping to identify the molecular targets of these new molecules (172, 174 – 177).”
Developing Pyrrole‐Derived Antimycobacterial Agents: a Rational Lead Optimization Approach
Biava, M., Porretta, G. C., Poce, G., Battilocchio, C., Alfonso, S., Logu, A. D., Manetti, F., & Botta, M. (2011) · ChemMedChem · doi:10.1002/cmdc.201000526 · Cited by 47
Musuka, S., Srivastava, S., Dona, C. W. S., Meek, C. C., Leff, R. D., Pasipanodya, J. G., & Gumbo, T. (2013) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00829-13 · Cited by 47
Nikiforov, P. O., Surade, S. B., Błaszczyk, M., et al. (2016) · Organic & Biomolecular Chemistry · doi:10.1039/c5ob02630j · Cited by 48
Gao, C., Peng, C., Shi, Y., You, X., Ran, K., Xiong, L., Ye, T.-H., Zhang, L., Wang, N., Zhu, Y., et al. (2016) · Scientific Reports · doi:10.1038/srep29717 · Cited by 48
New drugs for the treatment of Mycobacterium tuberculosis infection
AlMatar, M., AlMandeal, H., Var, İ., Kayar, B., & Köksal, F. (2017) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2017.04.105 · Cited by 49
Igarashi, M., Ishizaki, Y., & Takahashi, Y. (2017) · The Journal of Antibiotics · doi:10.1038/ja.2017.126 · Cited by 46
Ammerman, N. C., Swanson, R. V., Bautista, E. M., et al. (2018) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00636-18 · Cited by 48
“At the time when we began to specifically investigate the treatment-shortening potential of clofazimine, we had interest in comparing the activity of the drug directly, on a milligram-per-kilogram basis, with that of bedaquiline, which is administered at 25 mg/kg in preclinical mouse models of TB (31, 78).”
MethodThe unusual structure of Ruminococcin C1 antimicrobial peptide confers clinical properties
Roblin, C., Chiumento, S., Bornet, O., Nouailler, M., Müller, C. S., Jeannot, K., Basset, C., Kieffer‐Jaquinod, S., Couté, Y., Torelli, S., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2004045117 · Cited by 48
“K. Andries et al., A diarylquinoline drug active on the ATP synthase ofMycobacterium tuberculosis.”
BackgroundDhameliya, T. M., Patel, K. I., Tiwari, R., Vagolu, S. K., Panda, D., Sriram, D., & Chakraborti, A. K. (2020) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2020.104538 · Cited by 47
Belardinelli, J. M., & Morbidoni, H. R. (2012) · Molecular Microbiology · doi:10.1111/mmi.12005 · Cited by 48
“Isolation of resistant mutants and their characterization has been the traditional and most rewarding strategy to unveil genes involved in the action of anti-tubercular drugs both in clinical use and during the development of new molecules (Vilcheze et al., 2000; Andries et al., 2005).”
BackgroundPathak, R., Madapa, S., & Batra, S. (2006) · Tetrahedron · doi:10.1016/j.tet.2006.10.053 · Cited by 48
The Resurrection of Phenotypic Drug Discovery
Childers, W. E., Elokely, K. M., & Abou-Gharbia, M. A. (2020) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.0c00006 · Cited by 48
Li, D., Gao, N., Zhu, N., et al. (2015) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2015.09.072 · Cited by 47
Tuberculosis drug discovery and emerging targets
Mdluli, K. E., Kaneko, T., & Upton, A. M. (2014) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12459 · Cited by 48
Zhang, Y., Chang, K. C., Leung, C.-C., et al. (2012) · Emerging Microbes & Infections · doi:10.1038/emi.2012.18 · Cited by 47
Molecular Basis of Drug Resistance in Mycobacterium tuberculosis
Cohen, K. A., Bishai, W. R., & Pym, A. S. (2014) · Microbiology Spectrum · doi:10.1128/microbiolspec.mgm2-0036-2013 · Cited by 49
“BDQ binds to and inhibits the M. tuberculosis ATP synthase gene encoded by the essential gene atpE (Rv1305, MT1345) (127).”
BackgroundIdentification of a novel class of quinoline–oxadiazole hybrids as anti-tuberculosis agents
Jain, P. P., Degani, M. S., Raju, A., Anantram, A., Seervi, M., Sathaye, S. S., Ray, M., & Rajan, M. G. R. (2015) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2015.11.057 · Cited by 47
Activation of type II NADH dehydrogenase by quinolinequinones mediates antitubercular cell death
Heikal, A., Hards, K., Cheung, C., Menorca, A., Timmer, M. S. M., Stocker, B. L., & Cook, G. M. (2016) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkw244 · Cited by 47
Drug development against tuberculosis: Past, present and future
Vasava, M. S., Bhoi, M. N., Rathwa, S. K., Borad, M. A., Nair, S., & Patel, H. D. (2017) · Indian Journal of Tuberculosis · doi:10.1016/j.ijtb.2017.03.002 · Cited by 48
Cyclic di-GMP regulates Mycobacterium tuberculosis resistance to ethionamide
Zhang, H., Xu, Z., Jiang, H., Wu, F., He, X., Liu, Y., Guo, S., Li, Y., Bi, L., Deng, J., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-06289-7 · Cited by 47
Ferraris, D. M., Miggiano, R., Rossi, F., & Rizzi, M. (2018) · Pathogens · doi:10.3390/pathogens7010017 · Cited by 49
“[127] through whole-cell screening assays using diarylquinoline molecules and the discovery of the anti-TB properties of the natural compound griselimicyn of Streptomyces origin [128].”
MethodShin, J. S., Ragunathan, P., Sundararaman, L., Nartey, W., Kundu, S., Manimekalai, M. S. S., Bogdanović, N., Dick, T., & Grüber, G. (2018) · FEBS Journal · doi:10.1111/febs.14392 · Cited by 47
“This novel insight into BDQ-binding to Mtε is a new starting point to fine tune the effect of BDQ and thereby the blocking of coupling events for ATP synthesis in the TB drug target F-ATP synthase [19].”
BackgroundInfluentialZhang, A. T., Montgomery, M. G., Leslie, A. G. W., Cook, G. M., & Walker, J. E. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1817615116 · Cited by 47
Hards, K., Cheung, C., Waller, N. J. E., et al. (2022) · Communications Biology · doi:10.1038/s42003-022-03110-8 · Cited by 46
de Melo, C. S., Feng, T., van der Westhuyzen, R., Gessner, R. K., Street, L. J., Morgans, G. L., Warner, D. F., Moosa, A., Naran, K., Lawrence, N., et al. (2015) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2015.10.021 · Cited by 47
Gold, B. S., Roberts, J., Ling, Y., Quezada, L. A. L., Glasheen, J., Ballinger, E. A., Somersan-Karakaya, S., Warrier, T., Warren, J. D., & Nathan, C. (2015) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00803-15 · Cited by 45
“tuberculosis in vitro and in vivo (40, 41).”
BackgroundAppleton, D. R., Pearce, A. N., & Copp, B. R. (2010) · Tetrahedron · doi:10.1016/j.tet.2010.05.033 · Cited by 46
Rip Van Winkle Wakes Up: Development of Tuberculosis Treatment in the 21st Century
Burman, W. J. (2010) · Clinical Infectious Diseases · doi:10.1086/651487 · Cited by 46
“treatment [62].”
BackgroundInfluentialKaniga, K., Cirillo, D. M., Hoffner, S. E., et al. (2016) · Journal of Clinical Microbiology · doi:10.1128/jcm.01123-16 · Cited by 46
“Bedaquiline, a diarylquinoline antimycobacterial (2), has received accelerated/conditional approval for use based on phase II trials in the United States (2012), the European Union (2014), and 7 countries with high MDR-TB burden (3–8).”
BackgroundSelf-citationSonawane, A. D., Garud, D. R., Udagawa, T., et al. (2017) · Organic & Biomolecular Chemistry · doi:10.1039/c7ob02523h · Cited by 46
Clofazimine Exposure In Vitro Selects Efflux Pump Mutants and Bedaquiline Resistance
Ismail, N. A., Peters, R. P. H., Ismail, N. A., et al. (2019) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.02141-18 · Cited by 46
Egorova, A., Jackson, M., Gavrilyuk, V., & Makarov, V. (2021) · Medicinal Research Reviews · doi:10.1002/med.21798 · Cited by 48
Peng, C., Gao, C., Wang, N., You, X., Zhang, L., Zhu, Y., Xv, Y., Zuo, W., Ran, K., Deng, H., et al. (2015) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2015.02.061 · Cited by 45
Chitra, S., Paul, N., Muthusubramanian, S., Manisankar, P., Yogeeswari, P., & Sriram, D. (2011) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2011.07.046 · Cited by 45
Trends in discovery of new drugs for tuberculosis therapy
Riccardi, G., & Pasca, M. R. (2014) · The Journal of Antibiotics · doi:10.1038/ja.2014.109 · Cited by 45
Meermann, B., Bockx, M., Laenen, A., et al. (2011) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-011-5339-y · Cited by 45
Mycobacterium tuberculosis IMPDH in Complexes with Substrates, Products and Antitubercular Compounds
Makowska-Grzyska, M., Kim, Y., Gorla, S. K., Wei, Y., Mandapati, K., Zhang, M., Maltseva, N., Modi, G. P., Boshoff, H. I., Gu, M., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0138976 · Cited by 45
“Indeed, one of the first reported TB drugs, para-aminosalicylic acid, was recently shown to disrupt folate biosynthesis [8], while the newest TB drug, bedaquiline exerts its activity through inhibition of ATP synthesis [9].”
BackgroundDean, W. M., Šiaučiulis, M., Storr, T. E., et al. (2016) · Angewandte Chemie International Edition · doi:10.1002/anie.201602264 · Cited by 45
Robertson, G. T., Scherman, M. S., Bruhn, D. F., et al. (2016) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkw467 · Cited by 45
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. (2018) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd012918 · Cited by 45
Srivastava, S., Bimal, D., Bohra, K., et al. (2018) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2018.02.067 · Cited by 45
Current advances in the clinical development of anti-tubercular agents
Tetali, S. R., Kunapaeddi, E., Mailavaram, R. P., Singh, V., Borah, P., Deb, P. K., Venugopala, K. N., Hourani, W., & Tekade, R. K. (2020) · Tuberculosis · doi:10.1016/j.tube.2020.101989 · Cited by 45
Cooper, C. B. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm400381v · Cited by 43
Priorities in tuberculosis research
Onyebujoh, P., Rodriguez, W. R., & Mwaba, P. (2006) · The Lancet · doi:10.1016/s0140-6736(06)68385-2 · Cited by 45
Bellinzoni, M., Haouz, A., Graña, M., et al. (2006) · Protein Science · doi:10.1110/ps.062163406 · Cited by 45
“Sparked by the development of mycobacterial genomics (Cole et al. 1998), many efforts have been invested during the last few years in the identification and characterization of novel drug targets (Sharma et al. 2004; Andries et al. 2005).”
BackgroundIsmail, N. A., Omar, S. V., Ismail, N. A., & Peters, R. P. H. (2018) · Data in Brief · doi:10.1016/j.dib.2018.09.057 · Cited by 47
Advances in the design of combination therapies for the treatment of tuberculosis
Larkins‐Ford, J., & Aldridge, B. B. (2022) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2023.2157811 · Cited by 47
Keating, T. A., Newman, J. V., Olivier, N. B., Otterson, L. G., Andrews, B. M., Boriack‐Sjodin, P. A., Breen, J. N., Doig, P. C., Dumas, J., Gangl, E. T., et al. (2012) · ACS Chemical Biology · doi:10.1021/cb300316n · Cited by 44
Exploring rumen methanogen genomes to identify targets for methane mitigation strategies
Attwood, G. T., Altermann, E., Kelly, W. J., Leahy, S. C., Zhang, L., & Morrison, M. (2011) · Animal Feed Science and Technology · doi:10.1016/j.anifeedsci.2011.04.004 · Cited by 44
Albesa-Jové, D., Chiarelli, L. R., Makarov, V., Pasca, M. R., Urresti, S., Mori, G., Salina, E. G., Vocat, A., Comino, N., Mohorko, E., et al. (2014) · ACS Chemical Biology · doi:10.1021/cb500149m · Cited by 45
Mycobacterium abscessus subsp abscessus lung disease: ‘trouble ahead, trouble behind…’
Griffith, D. E. (2014) · F1000Prime Reports · doi:10.12703/p6-107 · Cited by 44
“abscessus subsp abscessus [26].”
Management of multidrug-resistant TB: novel treatments and their expansion to low resource settings
Sloan, D. J., & Lewis, J. M. (2016) · Transactions of the Royal Society of Tropical Medicine and Hygiene · doi:10.1093/trstmh/trv107 · Cited by 44
“30,31 Early clinical studies indicated high bactericidal activity against drug-susceptible and resistant disease; the most compelling evidence was from a multicentre phase II trial (TMC207-C208) in which a WHO-approved optimised background regimen (OBR) for pulmonary MDR-TB was supplemented, for…”
Synthesis and structure-activity studies of side chain analogues of the anti-tubercular agent, Q203
Kang, S., Kim, Y. M., Kim, R. Y., Seo, M. J., No, Z., Nam, K., Kim, S., & Kim, J. C. (2016) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2016.09.082 · Cited by 44
Ragunathan, P., Sielaff, H., Sundararaman, L., Biuković, G., Manimekalai, M. S. S., Singh, D., Kundu, S., Wohland, T., Frasch, W. D., Dick, T., et al. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.784959 · Cited by 44
“These data correlate with recent results (23, 24) that showed that ATP hydrolysis catalyzed by the M.”
BackgroundMethodResultInfluentialBedaquiline as a potential agent in the treatment ofMycobacterium abscessusinfections
Vesenbeckh, S. M., Schönfeld, N., Roth, A. J., et al. (2017) · European Respiratory Journal · doi:10.1183/13993003.00083-2017 · Cited by 44
Rehberg, N., Akoné, S. H., Ioerger, T. R., Erlenkamp, G., Δαλέτος, Γ., Gohlke, H., Proksch, P., & Kalscheuer, R. (2017) · ACS Infectious Diseases · doi:10.1021/acsinfecdis.7b00055 · Cited by 45
Triclosan and its derivatives as antimycobacterial active agents
Vosátka, R., Krátký, M., & Vinšová, J. (2017) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2017.12.013 · Cited by 44
Esmail, A., Sabur, N. F., Okpechi, I. G., & Dheda, K. U. J. (2018) · Journal of Thoracic Disease · doi:10.21037/jtd.2018.05.11 · Cited by 44
“This orally administrated medication acts via a novel mechanism that selectively inhibits mycobacterial adenosine triphosphate synthase (42,43).”
BackgroundA structural insight of bedaquiline for the cardiotoxicity and hepatotoxicity
Patel, H., Pawara, R. H., Pawara, K., Ahmed, F., Shirkhedkar, A. A., & Surana, S. J. (2019) · Tuberculosis · doi:10.1016/j.tube.2019.06.005 · Cited by 45
Radiosynthesis and PET Bioimaging of 76Br-Bedaquiline in a Murine Model of Tuberculosis
Ordoñez, A. A., Carroll, L. S., Abhishek, S., et al. (2019) · ACS Infectious Diseases · doi:10.1021/acsinfecdis.9b00207 · Cited by 44
“The reaction mixture was diluted with water (10 ml) and purified by semi-preparative HPLC, which was performed using a Phenomenex Luna C18(2) 10 μm, 250 × 4.”
MethodInfluentialOverview of DNA Sequencing Strategies
Shendure, J., Porreca, G. J., & Church, G. M. (2008) · Current Protocols in Molecular Biology · doi:10.1002/0471142727.mb0701s81 · Cited by 46
“…commercialization, 454 sequencing has contributed to successful projects over a range of applications, including bacterial genome resequencing (Andries et al., 2005; Velicer et al., 2006), de novo bacterial genome sequencing (best done as a combination of dideoxy- and pyrosequencingbased…”
BackgroundJacobowski, A. C., Boleti, A. P. D. A., Cruz, M. V., Santos, K. F. D. P., de Andrade, L. R. M., Frihling, B. E. F., Migliolo, L., Paiva, P. M. G., Teodoro, P. E., Teodoro, L. P. R., et al. (2025) · Pharmaceuticals · doi:10.3390/ph18081119 · Cited by 51
“Independent screens have high-lighted a large family of QcrB inhibitors, which are small molecules with high chemical diversity [82,83].”
Multimetallic Multifunctional Catalysts for Asymmetric Reactions
Shibasaki, M., Kanai, M., Matsunaga, S., & Kumagai, N. (2011) · Topics in organometallic chemistry · doi:10.1007/3418_2011_1 · Cited by 43
Ekins, S., Pottorf, R. S., Reynolds, R. C., Williams, A. J., Clark, A. M., & Freundlich, J. S. (2014) · Journal of Chemical Information and Modeling · doi:10.1021/ci500077v · Cited by 45
Salina, E. G., Riabova, O., Kaprelyants, A. S., & Makarov, V. (2013) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01308-13 · Cited by 43
“Despite the recent success with drug candidates such as diarylquinolines (TMC207), which target ATP synthesis (26, 27), and benzothiazinones (BTZ043), which target essential cell wall arabinan synthesis (28), the efficacies of both candidates at killing dormant bacilli were found to be low.”
Background
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
