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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.
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“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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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- It may state two separate claims as one. 40
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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.
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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.
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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.
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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.
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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.
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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.
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“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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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
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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]
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Flagged first, then by citations
Cited by
Sorted by citations
Items 101–200 of 2,159
Eswaran, S., Adhikari, A. V., Chowdhury, I. H., Pal, N. K., & Thomas, K. D. (2010) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2010.04.022 · Cited by 228
Haagsma, A. C., Abdillahi-Ibrahim, R., Wagner, M. J., Krab, K., Vergauwen, K., Guillemont, J., Andries, K., Lill, H., Koul, A., & Bald, D. (2008) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01393-08 · Cited by 230
“TMC207 has a strongly hydrophobic core structure (3) and may get trapped in the mitochondrial outer membrane.”
BackgroundInfluentialSelf-citationEnergetics of Respiration and Oxidative Phosphorylation in Mycobacteria
Cook, G. M., Hards, K., Vilchèze, C., Hartman, T., & Berney, M. (2014) · Microbiology Spectrum · doi:10.1128/microbiolspec.mgm2-0015-2013 · Cited by 212
“The most promising compounds clinically, the diarylquinolines, have been shown to target the F 1 F 0 -ATP synthase and inhibit ATP synthesis (109, 111, 112).”
BackgroundInfluentialBald, D., Villellas, C., Lü, P., & Koul, A. (2017) · mBio · doi:10.1128/mbio.00272-17 · Cited by 227
“throughput screening efforts have mainly yielded classes of small-molecule inhibitors active on either ATP synthase (8, 26) or the cytochrome bc1 complex (23, 25, 26).”
BackgroundStructure of mycobacterial ATP synthase bound to the tuberculosis drug bedaquiline
Guo, H., Courbon, G. M., Bueler, S. A., Mai, J., Liu, J., & Rubinstein, J. L. (2021) · Nature · doi:10.1038/s41586-020-3004-3 · Cited by 200
“b-δ (264-286) a (90-108) c (49-81) b' (30-48) b-δ (2-20) a (216-245) b' (30-63) c (53-80) BDQ-free BDQ-saturated”
A wearable haemodialysis device for patients with end-stage renal failure: a pilot study
Davenport, A., Gura, V., Ronco, C., Beizai, M., Ezon, C., & Rambod, E. (2007) · The Lancet · doi:10.1016/s0140-6736(07)61864-9 · Cited by 218
Huitric, E., Verhasselt, P., Koul, A., Andries, K., Hoffner, S. E., & Andersson, D. I. (2009) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01611-09 · Cited by 216
“model accelerates the bactericidal effect (4, 21), supporting the”
BackgroundInfluentialSelf-citationThe Macrophage: A Disputed Fortress in the Battle against Mycobacterium tuberculosis
Queval, C. J., Brosch, R., & Simeone, R. (2017) · Frontiers in Microbiology · doi:10.3389/fmicb.2017.02284 · Cited by 215
“Concerning drug treatment of TB, most of the drugs used today date from the 1950s to 1960s, with a few exceptions, such as bedaquiline, a recently discovered ATP synthase inhibitor (Andries et al., 2005) that is currently used successfully in drug regimens against MDR-TB (Diacon et al.”
BackgroundAlmeida, D. V., Ioerger, T. R., Tyagi, S. K., Li, S., Mdluli, K. E., Andries, K., Grosset, J. H. E., Sacchettini, J. C., & Nuermberger, E. L. (2016) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00753-16 · Cited by 218
“The principal mechanism of action of bedaquiline is inhibition of the mycobacterial ATP synthase (3, 4).”
BackgroundResultSelf-citationKadura, S., King, N. C., Nakhoul, M., Zhu, H., Theron, G., Köser, C. U., & Farhat, M. R. (2020) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkaa136 · Cited by 210
“Andries 2005;11!”
Daily Dosing of Rifapentine Cures Tuberculosis in Three Months or Less in the Murine Model
Rosenthal, I. M., Zhang, M., Williams, K. N., et al. (2007) · PLoS Medicine · doi:10.1371/journal.pmed.0040344 · Cited by 206
“For example, TMC-207 has been highly regarded as a candidate for shortening therapy [4], but is currently being developed as a drug for multidrug-resistant TB rather than for drugsusceptible disease, at least in part due to a drug–drug interaction with rifampin.”
BackgroundBedaquiline Resistance: Its Emergence, Mechanism, and Prevention
Nguyen, T. V. A., Anthony, R. M., Bañuls, A., Nguyen, T. V. A., Vu, D. H., & Alffenaar, J. C. (2017) · Clinical Infectious Diseases · doi:10.1093/cid/cix992 · Cited by 213
“The in vitro resistant mutations identified were all within the atpE gene [4].”
InfluentialCook, G. M., Berney, M., Gebhard, S., Heinemann, M., Cox, R. A., Danilchanka, O., & Niederweis, M. (2009) · Advances in microbial physiology/Advances in Microbial Physiology · doi:10.1016/s0065-2911(09)05502-7 · Cited by 226
“N IH -PA Author M anuscript N IH -PA Author M anuscript N IH -PA Author M anuscript (Andries et al., 2005; Koul et al., 2007).”
BackgroundInfluentialTmc207: the First Compound of A New class of Potent Anti-Tuberculosis Drugs
Matteelli, A., Carvalho, A. C., Dooley, K. E., & Kritski, A. L. (2010) · Future Microbiology · doi:10.2217/fmb.10.50 · Cited by 210
Interactions with Microbial Proteins Driving the Antibacterial Activity of Flavonoids
Donadio, G., Mensitieri, F., Santoro, V., Parisi, V., Bellone, M. L., Tommasi, N. D., Izzo, V., & Piaz, F. D. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13050660 · Cited by 237
“tuberculosis ATP synthase, has been approved by the United States Food and Drug Administration [77], and a few polyphenols such as resveratrol, piceatannol, quercetin, morin, and epicatechin were reported to inhibit E.”
BackgroundTian, J., Bryk, R., Itoh, M., Suematsu, M., & Nathan, C. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501605102 · Cited by 200
Mycobacterium ulcerans infection: control, diagnosis, and treatment
Sizaire, V., Nackers, F., Comte, É., et al. (2006) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(06)70464-9 · Cited by 200
Li, W., Upadhyay, A., Fontes, F. L., North, E. J., Wang, Y., Crans, D. C., Grzegorzewicz, A. E., Jones, V., Franzblau, S. G., Lee, R. E., et al. (2014) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.03229-14 · Cited by 202
Miniaturizing chemistry and biology in microdroplets
Kelly, B. T., Baret, J., Taly, V., & Griffiths, A. D. (2007) · Chemical Communications · doi:10.1039/b616252e · Cited by 202
Mycobacterium tuberculosis Wears What It Eats
Russell, D. G., VanderVen, B. C., Lee, W., Abramovitch, R. B., Kim, M., Homolka, S., Niemann, S., & Rohde, K. H. (2010) · Cell Host & Microbe · doi:10.1016/j.chom.2010.06.002 · Cited by 198
“New drugs that exploit targets relevant to bacterial metabolism within the host are required, one such example are the new ATP synthase inhibitors that impact both growing and vegetative bacteria (Andries et al., 2005).”
BackgroundSchmitt, E. K., Riwanto, M., Sambandamurthy, V. K., Roggo, S. P., Miault, C., Zwingelstein, C., Krastel, P., Noble, C. G., Beer, D., Rao, S. P. S., et al. (2011) · Angewandte Chemie International Edition · doi:10.1002/anie.201101740 · Cited by 194
New drug candidates and therapeutic targets for tuberculosis therapy
Zhang, Y., Post-Martens, K., & Denkin, S. M. (2006) · Drug Discovery Today · doi:10.1016/s1359-6446(05)03626-3 · Cited by 194
The Cyclic Peptide Ecumicin Targeting ClpC1 Is Active against Mycobacterium tuberculosis In Vivo
Gao, W., Kim, J. Y., Anderson, J. R., Akopian, T. N., Hong, S., Jin, Y.-Y., Kandror, O., Kim, J., Lee, I.-A., Lee, S.-Y., et al. (2014) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.04054-14 · Cited by 194
“Attempts to discover new TB drugs and targets via large-scale screening against intact mycobacteria have largely been confined to synthetic compound libraries and to date have yielded only one new clinical TB drug, the diarylquinoline bedaquiline (6, 7).”
BackgroundTasneen, R., Li, S., Peloquin, C. A., et al. (2011) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.05293-11 · Cited by 194
“licating and nonreplicating organisms in vitro (5, 16, 26).”
BackgroundSelf-citationTargeting Antibiotic Tolerance, Pathogen by Pathogen
Meylan, S., Andrews, I. W., & Collins, J. J. (2018) · Cell · doi:10.1016/j.cell.2018.01.037 · Cited by 194
“Bedaquiline also inhibits ATP production, but via direct targeting of the mycobacterial ATP synthase (Andries et al., 2005).”
Challenges of antibacterial discovery revisited
Gwynn, M. N., Portnoy, A., Rittenhouse, S. F., & Payne, D. J. (2010) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2010.05828.x · Cited by 197
“Omics”-Informed Drug and Biomarker Discovery: Opportunities, Challenges and Future Perspectives
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“The discovery of diarylquinolones targeting the mycobacterial ATP synthase, for example, demonstrated how sequence diversity can be exploited to target pathways perceived to be ubiquitous [23].”
BackgroundUpdate on the Treatment of Tuberculosis and Latent Tuberculosis Infection
Blumberg, H. M. (2005) · JAMA · doi:10.1001/jama.293.22.2776 · Cited by 191
Kalia, N. P., Hasenoehrl, E., Rahman, N. B. A., Koh, V. H. Q., Ang, M. L. T., Sajorda, D. R., Hards, K., Grüber, G., Alonso, S., Cook, G. M., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1706139114 · Cited by 189
Targeting Bacterial Central Metabolism for Drug Development
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“the F0F1 ATP synthase (Andries et al., 2005; Koul et al., 2007).”
BackgroundGuglielmetti, L., Dû, D. L., Jachym, M. F., et al. (2014) · Clinical Infectious Diseases · doi:10.1093/cid/ciu786 · Cited by 188
“thase [6].”
Self-citationEfflux Inhibition with Verapamil Potentiates Bedaquiline in Mycobacterium tuberculosis
Gupta, S., Cohen, K. A., Winglee, K., et al. (2013) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01462-13 · Cited by 186
“A diarylquinoline, bedaquiline inhibits the mycobacterial proton pump, ATP synthase (9).”
BackgroundThe chemotherapy of tuberculosis: past, present and future [State of the art]
Mitchison, D. A., & Davies, G. (2012) · The International Journal of Tuberculosis and Lung Disease · doi:10.5588/ijtld.12.0083 · Cited by 194
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New Insights in to the Intrinsic and Acquired Drug Resistance Mechanisms in Mycobacteria
Nasiri, M. J., Haeili, M., Ghazi, M., Goudarzi, H., Pormohammad, A., Fooladi, A. A. I., & Feizabadi, M. M. (2017) · Frontiers in Microbiology · doi:10.3389/fmicb.2017.00681 · Cited by 191
“It binds to and inhibits the mycobacterial ATP synthase encoded by the essential gene atpE (Andries et al., 2005).”
BackgroundUpdate on the epidemiology, diagnosis, and treatment of leprosy
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Self-citationThe Tuberculosis Drug Discovery and Development Pipeline and Emerging Drug TargetsPreprint
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“ATP synthesis and PMF generation are among the best-validated Mtb drug targets owing to the clinical successes of the ATP synthase inhibitor TMC207 (bedaquiline, Sirturo) (Andries et al. 2005; Diacon et al. 2009) and the cornerstone TB drug pyrazinamide, which disrupts the PMF (Zhang et al.”
BackgroundIdentification of Novel Imidazo[1,2-a]pyridine Inhibitors Targeting M. tuberculosis QcrB
Abrahams, K. A., Cox, J. A. G., Spivey, V. L., Loman, N. J., Pallen, M. J., Constantinidou, C., Fernández, R., Alemparte, C., Remuiñán, M. J., Barros, D., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0052951 · Cited by 177
“identified utilizing a whole cell phenotypic HTS campaign of a library of more than 70,000 compounds against Mycobacterium smegmatis [11,12,13].”
MethodKang, S., Kim, R. Y., Seo, M. J., Lee, S., Kim, Y. M., Seo, M., Seo, J. J., Ko, Y., Choi, I., Jang, J., et al. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm5003606 · Cited by 178
New Small-Molecule Synthetic Antimycobacterials
Ballell, L., Field, R. A., Duncan, K., & Young, R. J. (2005) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.49.6.2153-2163.2005 · Cited by 181
“7 Yes 5 steps/ 200/ SAR Candidate (3) VOL.”
BackgroundTuberculosis drug discovery in the post‐post‐genomic era
Lechartier, B., Rybniker, J., Zumla, A. I., & Cole, S. T. (2014) · EMBO Molecular Medicine · doi:10.1002/emmm.201201772 · Cited by 169
“In 2005, using a classical phenotypic screen, Andries et al (2005) discovered a very potent molecule, TMC207 or bedaquiline, an innovative, recently-approved drug candidate that offers considerable hope for curing MDR-TB cases.”
Synergistic Activity of R207910 Combined with Pyrazinamide against Murine Tuberculosis
Ibrahim, M., Andries, K., Lounis, N., et al. (2006) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00898-06 · Cited by 175
“R207910 (also known as TMC207) belongs to a new family of antituberculosis drugs, the diarylquinolines (1).”
BackgroundResultInfluentialSelf-citationHameed, H. M. A., Islam, M. M., Chhotaray, C., Wang, C., Liu, Y., Tan, Y., Li, X., Tan, S., Delorme, V., Yew, W. W., et al. (2018) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2018.00114 · Cited by 179
“BDQ has a favored specificity toward the mycobacterial ATP synthase, as compared to mitochondrial ATP synthase in exerting its therapeutic action (Haagsma et al., 2009), but the mutations in AtpE (A63P and I66M) disturbs such inhibition against bacterial ATP synthase C.”
BackgroundTuberculosis: The drug development pipeline at a glance
Villemagne, B., Crauste, C., Flipo, M., Baulard, A. R., Deprez, B. P., & Willand, N. (2012) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2012.02.033 · Cited by 179
In Vitro Antimycobacterial Spectrum of a Diarylquinoline ATP Synthase Inhibitor
Huitric, E., Verhasselt, P., Andries, K., & Hoffner, S. (2007) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00181-07 · Cited by 173
“These results are in line with earlier reported values for seven MAC strains (1) and”
BackgroundResultInfluentialSelf-citationAntiinfectives targeting enzymes and the proton motive force
Feng, X., Zhu, W., Schurig-Briccio, L. A., Lindert, S., Shoen, C. M., Hitchings, R., Li, J., Wang, Y., Baig, N., Zhou, T. H., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1521988112 · Cited by 173
“More recently, the analog 1-(2-adamantyl)-3-(2,3,4-trifluorophenyl)urea [AU1235 (9)] has been found to kill replicating but not nonreplicating M.”
BackgroundMethodResultInfluentialINCIDENCE OF POLARIZING FOREIGN BODIES IN LUNG BIOPSIES OF PATIENTS WITH PULMONARY SARCOIDOSIS
Sharma, V. K., Djekidel, K., Haber, M. M., & Haber, A. D. (2006) · CHEST Journal · doi:10.1378/chest.130.1.261 · Cited by 170
Totally drug‐resistant tuberculosis and adjunct therapies
Parida, S. K., Axelsson‐Robertson, R., Rao, M., Singh, N., Master, I., Lutckii, A. A., Keshavjee, S. A., Andersson, J., Zumla, A. I., & Maeurer, M. J. (2014) · Journal of Internal Medicine · doi:10.1111/joim.12264 · Cited by 171
Outwitting Evolution: Fighting Drug-Resistant TB, Malaria, and HIV
Goldberg, D. E., Siliciano, R. F., & Jacobs, W. R. (2012) · Cell · doi:10.1016/j.cell.2012.02.021 · Cited by 168
Cross‐species chemogenomic profiling reveals evolutionarily conserved drug mode of action
Kapitzky, L., Beltrão, P., Berens, T. J., Gassner, N. C., Zhou, C., Wüster, A., Wu, J. T.-Y., Babu, M. M., Elledge, S. J., Toczyski, D. P., et al. (2010) · Molecular Systems Biology · doi:10.1038/msb.2010.107 · Cited by 166
“…studies of gene expression changes after treatment with a small molecule (Hughes et al, 2000; Lamb et al, 2006), physical isolation of a drug–target complex through affinity chromatography (Rix and Superti-Furga, 2009) and whole-genome sequencing of drug-resistant strains (Andries et al, 2005).”
BackgroundNew Tuberculosis Therapeutics: A Growing Pipeline
Spigelman, M. (2007) · The Journal of Infectious Diseases · doi:10.1086/518663 · Cited by 169
“[19] first described the work done by Johnson & Johnson on the research and development of TMC207 (then referred to as “R207910”), a novel diarylquinoline, for potential use in the treatment of TB.”
BackgroundAn overview of new antitubercular drugs, drug candidates, and their targets
Bahuguna, A., & Rawat, D. S. (2019) · Medicinal Research Reviews · doi:10.1002/med.21602 · Cited by 179
“Bedaquiline blocks these ion‐binding sites thereby interfering with the proton pump which results in decreased intracellular ATP levels.(25,30) A recent study suggested that in addition to the c subunit, bedaquiline also targets the ε subunit of F‐ATP synthase by interacting with Trp16 residue.”
BackgroundLienhardt, C., Raviglione, M. C., Spigelman, M., Hafner, R., Jaramillo, E., Höelscher, M., Zumla, A. I., & Gheuens, J. (2012) · The Journal of Infectious Diseases · doi:10.1093/infdis/jis034 · Cited by 173
“Two novel drugs are presently entering into phase 3 trials for the treatment of MDR tuberculosis: TMC-207 (bedaquiline), a novel adenosine triphosphate synthase inhibitor [8], and OPC-67683 (delamanid), a member of the nitroimidazole family (nitroimido-oxazole subclass) [9].”
New tuberculosis drug targets, their inhibitors, and potential therapeutic impact
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“diaryquinolones) in the same class of agent.(2,3) Many patients, however, have shown cross-resistance within this class, suggesting that previous administration of older fluoroquinolones may have a negative impact on the effectiveness of new compounds.”
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“Targeting ATP biosynthesis The recent discovery of an ATP synthase inhibitor (R207910) validates ATP biosynthesis as a target for antibiotic discovery [84 ].”
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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
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