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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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THE F0F1-TYPE ATP SYNTHASES OF BACTERIA: Structure and Function of the F0 Complex
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Intracellular pH regulation by Mycobacterium smegmatis and Mycobacterium bovis BCG
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Flagged first, then by citations
Cited by
Sorted by citations
Items 201–300 of 2,159
New anti-tuberculosis drugs in clinical trials with novel mechanisms of action
Rivers, E. C., & Mancera, R. L. (2008) · Drug Discovery Today · doi:10.1016/j.drudis.2008.09.004 · Cited by 141
Remuiñán, M. J., Pérez‐Herrán, E., Rullás, J., Alemparte, C., Martínez-Hoyos, M., Dow, D. J., Afari, J., Mehta, N., Esquivias, J., Jiménez, E., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0060933 · Cited by 137
“The often attractive anti-tubercular properties of these molecules have also spurred interest in mode of action (MoA) studies, leading to the postulation of new hypotheses for benzothiazinones [12], bedaquiline [8], PA-824 [13], SQ-109 [14], BM212 [15], adamantyl ureas [16] and benzimidazole C215 [17].”
BackgroundZimenkov, D. V., Nosova, E. Y., Kulagina, E. V., et al. (2017) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkx094 · Cited by 139
Altaf, M., Miller, C. H., Bellows, D. S., et al. (2010) · Tuberculosis · doi:10.1016/j.tube.2010.09.002 · Cited by 138
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“Consequently, there has been considerable excitement about the recently developed compounds PA824 and bedaquiline (TMC-207) [6, 7].”
Direct inhibitors of InhA are active against Mycobacterium tuberculosis
Manjunatha, U. H., Rao, S. P. S., Kondreddi, R. R., et al. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.3010597 · Cited by 137
Lienhardt, C., Vernon, A., & Raviglione, M. C. (2010) · Current Opinion in Pulmonary Medicine · doi:10.1097/mcp.0b013e328337580c · Cited by 137
Genetic Basis of Growth Adaptation of Escherichia coli after Deletion of pgi, a Major Metabolic Gene
Charusanti, P., Conrad, T. M., Knight, E. M., Venkataraman, K., Fong, N. L., Xie, B., Gao, Y., & Palsson, B. Ø. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1001186 · Cited by 135
In Vitro Interactions between New Antitubercular Drug Candidates SQ109 and TMC207
Reddy, V. M., Einck, L., Andries, K., & Nacy, C. A. (2010) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01601-09 · Cited by 134
“TMC207 (also known as R207910) is a diarylquinoline that specifically inhibits mycobacteria by inhibition of ATP synthesis (2).”
BackgroundInfluentialSelf-citationInflammation in tuberculosis: interactions, imbalances and interventions
Kaufmann, S. H. E., & Dorhoi, A. (2013) · Current Opinion in Immunology · doi:10.1016/j.coi.2013.05.005 · Cited by 138
Next-generation sequencing: applications beyond genomes
Marguerat, S., Wilhelm, B. T., & Bähler, J. (2008) · Biochemical Society Transactions · doi:10.1042/bst0361091 · Cited by 138
“The latter example illustrates that the power of next-generation sequencing is increasingly exploited to re-sequence strains and individuals for which reference genome sequences are availabletosamplegenomicdiversity.Suchstudieshaveidentified mutations in bacterial strains [ 22 ,23], polymorphisms in worm [24], structu…”
BackgroundProbing the Interaction of the Diarylquinoline TMC207 with Its Target Mycobacterial ATP Synthase
Haagsma, A. C., Podasca, I., Koul, A., Andries, K., Guillemont, J., Lill, H., & Bald, D. (2011) · PLoS ONE · doi:10.1371/journal.pone.0023575 · Cited by 141
Self-citationSatta, G., Lipman, M. C. I., Smith, G. P., Arnold, C., Kon, O. M., & McHugh, T. D. (2017) · Clinical Microbiology and Infection · doi:10.1016/j.cmi.2017.10.030 · Cited by 131
“It has been successfully used to determine the target of bedaquiline (BDQ) [33].”
MethodOverview of DNA Sequencing Strategies
Shendure, J., Porreca, G. J., Church, G. M., Gardner, A. F., Hendrickson, C. L., Kieleczawa, J., & Slatko, B. E. (2011) · Current Protocols in Molecular Biology · doi:10.1002/0471142727.mb0701s96 · Cited by 136
Targeting Phenotypically Tolerant Mycobacterium tuberculosis
Gold, B. S., & Nathan, C. (2017) · Microbiology Spectrum · doi:10.1128/microbiolspec.tbtb2-0031-2016 · Cited by 134
Lipid droplets: a cellular organelle vital in cancer cells
Jin, Y., Tan, Y., Wu, J., & Ren, Z. (2023) · Cell Death Discovery · doi:10.1038/s41420-023-01493-z · Cited by 150
Increasing the structural coverage of tuberculosis drug targets
Baugh, L., Phan, I. Q., Begley, D. W., Clifton, M. C., Armour, B. L., Dranow, D. M., Taylor, B. M., Muruthi, M. M., Abendroth, J. A., Fairman, J. W., et al. (2014) · Tuberculosis · doi:10.1016/j.tube.2014.12.003 · Cited by 128
“tuberculosis, and targets ATP synthases in both species (proteins sharing 92% sequence identity) [20].”
BackgroundJi, X., Huang, H., Li, Y., et al. (2012) · Angewandte Chemie International Edition · doi:10.1002/anie.201202412 · Cited by 130
Cook, G. M., Hards, K., Dunn, E. A., Heikal, A., Nakatani, Y., Greening, C., Crick, D. C., Fontes, F. L., Pethe, K., Hasenoehrl, E., et al. (2017) · Microbiology Spectrum · doi:10.1128/microbiolspec.tbtb2-0014-2016 · Cited by 131
“Several new antitubercular compounds have been reported that target oxidative phosphorylation in mycobacteria (11, 20, 88).”
BackgroundInfluentialAntituberculosis Drug Research: A Critical Overview
Beena, & Rawat, D. S. (2012) · Medicinal Research Reviews · doi:10.1002/med.21262 · Cited by 129
Discovery of Selective Menaquinone Biosynthesis Inhibitors against Mycobacterium tuberculosis
Debnath, J., Siricilla, S., Wan, B., Crick, D. C., Lenaerts, A. J. M., Franzblau, S. G., & Kurosu, M. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm201608g · Cited by 128
The within-host population dynamics of Mycobacterium tuberculosis vary with treatment efficacy
Trauner, A., Liu, Q., Via, L. E., Liu, X., Ruan, X., Liang, L., Shi, H., Chen, Y., Wang, Z., Liang, R., et al. (2017) · Genome biology · doi:10.1186/s13059-017-1196-0 · Cited by 126
Nitazoxanide Kills Replicating and Nonreplicating Mycobacterium tuberculosis and Evades Resistance
de Carvalho, L. P. S., Lin, G., Jiang, X., et al. (2009) · Journal of Medicinal Chemistry · doi:10.1021/jm9010719 · Cited by 128
Energetics of Pathogenic Bacteria and Opportunities for Drug Development
Cook, G. M., Greening, C., Hards, K., & Berney, M. (2014) · Advances in microbial physiology/Advances in Microbial Physiology · doi:10.1016/bs.ampbs.2014.08.001 · Cited by 129
The DprE1 enzyme, one of the most vulnerable targets of Mycobacterium tuberculosis
Riccardi, G., Pasca, M. R., Chiarelli, L. R., Manina, G., Mattevi, A., & Binda, C. (2013) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-013-5218-x · Cited by 130
“This drug inhibits the C subunit of essential enzyme ATP synthase (Andries et al. 2005).”
BackgroundMethodArora, K., Ochoa‐Montaño, B., Tsang, P. S., Blundell, T. L., Dawes, S. S., Mizrahi, V., Bayliss, T., Mackenzie, C. J., Cleghorn, L. A. T., Ray, P. C., et al. (2014) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.03486-14 · Cited by 127
“This diarylquinoline drug is thought to target the Mycobacterium tuberculosis ATP synthase, a critical component of mycobacterial energy metabolism (2).”
BackgroundTuberculosis Immunopathology: The Neglected Role of Extracellular Matrix Destruction
Elkington, P. T., D'Armiento, J. M., & Friedland, J. S. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3001847 · Cited by 127
2-(2-Hydrazinyl)thiazole derivatives: Design, synthesis and in vitro antimycobacterial studies
Makam, P., Ramakrishna, K., Prakash, A., & Kannan, T. (2013) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2013.08.054 · Cited by 128
Lechartier, B., Hartkoorn, R. C., & Cole, S. T. (2012) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01476-12 · Cited by 126
“As DprE1 is involved in the synthesis of arabinan, an integral component of the bacterial cell wall, we hypothesize that sub-MICs of BTZ043 weaken the bacterial cell wall and allow improved penetration of TMC207 to its target, ATP synthase (1).”
BackgroundSimple Model for Testing Drugs against Nonreplicating Mycobacterium tuberculosis
Sala, C., Dhar, N., Hartkoorn, R. C., Zhang, M., Ha, Y. H., Schneider, P. A., & Cole, S. T. (2010) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00821-10 · Cited by 130
“Neither INH nor BTZ043 affected resazurin reduction, whereas a marked concentration-dependent decrease in fluorescence was seen with RIF (activity starting at 370 ng/ml), MOXI ( 1 g/ml), PA-824 ( 1 g/ml), and TMC207 ( 370 ng/ml) (Fig.”
BackgroundInfluentialDrug resistance mechanisms and drug susceptibility testing for tuberculosis
Miotto, P., Zhang, Y., Cirillo, D. M., & Yam, W. C. (2018) · Respirology · doi:10.1111/resp.13393 · Cited by 125
Emergence of bedaquiline resistance in a high tuberculosis burden country
Chesov, E., Chesov, D., Maurer, F. P., et al. (2021) · European Respiratory Journal · doi:10.1183/13993003.00621-2021 · Cited by 126
Recent advances in the diagnosis and treatment of multidrug-resistant tuberculosis
Ahmad, S., & Mokaddas, E. M. (2009) · Respiratory Medicine · doi:10.1016/j.rmed.2009.07.010 · Cited by 126
Addition of PNU-100480 to First-Line Drugs Shortens the Time Needed to Cure Murine Tuberculosis
Williams, K. N., Brickner, S. J., Stover, C. K., et al. (2009) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200904-0611oc · Cited by 125
Multidrug-Resistant Tuberculosis
Sharma, S. K., & Mohan, A. (2006) · CHEST Journal · doi:10.1016/s0012-3692(15)50981-1 · Cited by 125
Fiorillo, M., Lamb, R., Tanowitz, H. B., Cappello, A. R., Martinez‐Outschoorn, U., Sotgia, F., & Lisanti, M. P. (2016) · Aging · doi:10.18632/aging.100983 · Cited by 127
“During our continued search for FDA-approved drugs that may behave as mitochondrial inhibitors, we identified bedaquiline, an antibiotic that was originally developed to block the bacterial ATP-synthase of multi-drug resistant pulmonary tuberculosis (TB) [13-15].”
de Jonge, M. R., Koymans, L. M. H., Guillemont, J., Koul, A., & Andries, K. (2007) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.21376 · Cited by 124
“occurs on the c-subunit of the F0 portion of the enzyme, encoded by the atpE gene.(2) Technically, it is very difficult to crystallize membranebound proteins and at present no crystal structures of the”
BackgroundSelf-citationBedaquiline for the treatment of resistant tuberculosis: Promises and pitfalls
Kakkar, A. K., & Dahiya, N. (2014) · Tuberculosis · doi:10.1016/j.tube.2014.04.001 · Cited by 124
“In addition, the bactericidal activity demonstrated by the RHZ after 2 months of treatment was paralleled by bedaquiline containing combinations with HZ and RZ after just 1 month of treatment [15].”
MethodRifampicin and rifapentine significantly reduce concentrations of bedaquiline, a new anti-TB drug
Svensson, E. M., Murray, S. R., Karlsson, M. O., & Dooley, K. E. (2014) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dku504 · Cited by 130
Onajole, O. K., Pieroni, M., Tipparaju, S. K., et al. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm4003878 · Cited by 124
Perspectives on Advances in Tuberculosis Diagnostics, Drugs, and Vaccines
Schito, M. L., Migliori, G. B., Fletcher, H. A., et al. (2015) · Clinical Infectious Diseases · doi:10.1093/cid/civ609 · Cited by 123
“Bedaquiline selectively targets the proton pump of adenosine triphosphate (ATP) synthesis, leading to inadequate ATP [48].”
BackgroundInfluentialSegala, E., Sougakoff, W., Chauffour, A., Jarlier, V., & Petrella, S. (2012) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.06154-11 · Cited by 133
“Six distinct mutations, Asp28¡Gly, Asp28¡Ala, Leu59¡Val, Glu61¡Asp, Ala63¡Pro, and Ile66¡Met, have been identified in the subunit c forming a C ring in the ATP synthase.”
BackgroundResultInfluentialSelf-citationCurrent Status and Research Strategies in Tuberculosis Drug Development
Dover, L. G., & Coxon, G. D. (2011) · Journal of Medicinal Chemistry · doi:10.1021/jm200305q · Cited by 120
Tantry, S. J., Markad, S. D., Shinde, V. N., Bhat, J., Balakrishnan, G., Gupta, A. K., Ambady, A., Raichurkar, A. V., Kedari, C. K., Sharma, S., et al. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b01358 · Cited by 125
Dupont, C., Viljoen, A. J., Thomas, S. S., Roquet, F., Herrmann, J., Pethe, K., & Kremer, L. (2017) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01225-17 · Cited by 124
“The genes sequenced included atpE (9, 10), atpC (13), and pepQ (43), as well as three”
BackgroundŠenerović, L., Opsenica, D., Morić, I., Aleksić, I., Spasić, M., & Vasiljević, B. (2019) · Advances in experimental medicine and biology · doi:10.1007/5584_2019_428 · Cited by 127
Borisov, V. B., Siletsky, S. A., Paiardini, A., Hoogewijs, D., Forte, E., Giuffrè, A., & Poole, R. K. (2020) · Antioxidants and Redox Signaling · doi:10.1089/ars.2020.8039 · Cited by 121
“The activity of BDQ appears to be specific for mycobacteria and is not observed with non-mycobacterial strains (4).”
Guerrero-Bustamante, C. A., Dedrick, R. M., Garlena, R. A., Russell, D. A., & Hatfull, G. F. (2021) · mBio · doi:10.1128/mbio.00973-21 · Cited by 124
“New antibiotics, including bedaquiline (7), have been developed, but the”
BackgroundUpadhayaya, R. S., Vandavasi, J. K., Vasireddy, N. R., et al. (2009) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2009.02.026 · Cited by 122
Treatment of latent infection withMycobacterium tuberculosis: update 2010
Leung, C. C., Rieder, H. L., Lange, C. G., & Yew, W. W. (2010) · European Respiratory Journal · doi:10.1183/09031936.00079310 · Cited by 121
Mak, P. A., Rao, S. P. S., Tan, M. P., Lin, X., Chyba, J., Tay, J. A., Ng, S. H., Tan, B. H., Cherian, J., Duraiswamy, J., et al. (2012) · ACS Chemical Biology · doi:10.1021/cb2004884 · Cited by 121
A Review of the Evidence for Using Bedaquiline (TMC207) to Treat Multi-Drug Resistant Tuberculosis
Fox, G. J., & Menzies, D. (2013) · Infectious Diseases and Therapy · doi:10.1007/s40121-013-0009-3 · Cited by 124
“Bedaquiline is given orally, reaching peak concentration 5 h after administration [14].”
BackgroundMethodInfluentialA small-molecule allosteric inhibitor of Mycobacterium tuberculosis tryptophan synthase
Wellington, S., Nag, P. P., Michalska, K., Johnston, S. E., Jedrzejczak, R. P., Kaushik, V. K., Clatworthy, A. E., Siddiqi, N., McCarren, P. R., Bajrami, B., et al. (2017) · Nature Chemical Biology · doi:10.1038/nchembio.2420 · Cited by 118
Chaturvedi, V., Dwivedi, N., Tripathi, R. P., et al. (2007) · The Journal of General and Applied Microbiology · doi:10.2323/jgam.53.333 · Cited by 120
Tyagi, S. K., Ammerman, N. C., Li, S., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1416951112 · Cited by 119
“tuberculosis (10), curiously like bedaquiline (11), which also exhibits limited EBA that is not evident until at least 4–5 d of treatment (12).”
BackgroundLü, P., Heineke, M. H., Koul, A., Andries, K., Cook, G. M., Lill, H., van Spanning, R. J. M., & Bald, D. (2015) · Scientific Reports · doi:10.1038/srep10333 · Cited by 123
Self-citationRecent advancements in the development of anti-tuberculosis drugs
Chetty, S., Ramesh, M., Singh, P., & Soliman, M. E. S. (2016) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2016.11.084 · Cited by 123
The F 1 F o -ATP Synthase of Mycobacterium smegmatis Is Essential for Growth
Tran, S. L., & Cook, G. M. (2005) · Journal of Bacteriology · doi:10.1128/jb.187.14.5023-5028.2005 · Cited by 116
“Several new antitubercular drugs have recently been reported (1, 30).”
BackgroundNew approaches to antimicrobial discovery
Lewis, K. (2016) · Biochemical Pharmacology · doi:10.1016/j.bcp.2016.11.002 · Cited by 126
Grosset, J. H. E., Singer, T. G., & Bishai, W. R. (2012) · The International Journal of Tuberculosis and Lung Disease · doi:10.5588/ijtld.12.0277 · Cited by 119
Verapamil Targets Membrane Energetics in Mycobacterium tuberculosis
Chen, C., Gardete, S., Jansen, R. S., Shetty, A., Dick, T., Rhee, K. Y., & Dartois, V. A. (2018) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.02107-17 · Cited by 117
“We observed that verapamil synergized with the oxidative 77 phosphorylation targeting drugs bedaquiline (F1Fo ATP-synthase (20)) and clofazimine (NADH 78”
Basso, L. A., da Silva, L. P., Fett‐Neto, A. G., de Azevedo, W. F., Moreira, Í. D. S., Palma, M. S., Calixto, J. Β., Filho, S. A., dos Santos, R. R., Soares, M. B. P., et al. (2005) · Memórias do Instituto Oswaldo Cruz · doi:10.1590/s0074-02762005000600001 · Cited by 118
Bedaquiline: A Novel Antitubercular Agent for the Treatment of Multidrug‐Resistant Tuberculosis
Worley, M. V., & Estrada, S. J. (2014) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1002/phar.1482 · Cited by 115
“tuberculosis strain does not confer cross-resistance relative to many other antitubercular agents, including isoniazid, rifampin, streptomycin, amikacin, ethambutol, and moxifloxacin.(13)”
BackgroundInfluentialATP synthase in mycobacteria: Special features and implications for a function as drug target
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“tuberculosis, both in vitro (33, 34) and in vivo (32, 35), and it has been hypothesized that this delay is related to bedaquiline’s mechanism of action targeting ATP synthase (36), with bactericidal activity evident only after bacterial energy stores have been depleted (33).”
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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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