TBAJ-876 

TBAJ-876 is an orally active diarylquinoline anti-Mycobacterium agent. TBAJ-876 regulates energy metabolism by targeting the c and ε subunits of Mycobacterium tuberculosis F-ATP synthase, exerts bactericidal activity against replicating Mycobacterium tuberculosis, and retains activity against strains carrying the Rv0678 mutation. TBAJ-876 undergoes N-demethylation in vivo to form its major active metabolite TBAJ-876-M3, which has lower lipophilicity and hERG potassium channel binding affinity. TBAJ-876 is well tolerated in BALB/c mice and significantly reduces the colony-forming units of Mycobacterium tuberculosis in the lungs. In addition, TBAJ-876 exhibits inhibitory activity against Mycobacterium abscessus, reduces bacterial loads in the lungs and spleens of infected mice, and shows no antagonistic effect when used in combination with common antibiotics. TBAJ-876 can be used in studies related to tuberculosis and Mycobacterium abscessus pulmonary diseases^[1][2].

TBAJ-876 (0.004-0.016 mg/L) has potent in vitro bacteriostatic activity against Mycobacterium tuberculosis H37Rv (MIC 0.008-0.016 mg/L) and Mycobacterium tuberculosis Beijing VN 2002-1585 (MIC 0.004 mg/L)^[1].
TBAJ-876 (0.0001-0.016 mg/L; 10 days) shows no interaction with its metabolite M3 when tested against Mycobacterium tuberculosis Beijing VN 2002-1585^[1].
TBAJ-876 (0.00025-0.063 mg/L; 1-6 days) demonstrates time- and concentration-dependent bactericidal activity against actively replicating Mycobacterium tuberculosis H37Rv, with the highest tested concentration (0.063 mg/L) reducing bacterial load to undetectable levels by day 6^[1].
TBAJ-876 (0.00025-0.063 mg/L; up to 21 days) has limited activity against nonreplicating Mycobacterium tuberculosis H37Rv, with only the highest tested concentration (0.063 mg/L, 16× MIC) reducing bacterial load by ~1.6 log₁₀ CFU/mL over 3 weeks^[1].
TBAJ-876 (1.38-138 μM; 5 days) exerts bacteriostatic activity against M. abscessus Bamboo in vitro at concentrations of 3x, 30x, and 300x its MIC, inhibiting growth without reducing bacterial counts below the initial inoculum^[2].
TBAJ-876 (0-2 μM; 3 days) exhibits additive or synergistic in vitro interactions with commonly used anti-M. abscessus antibiotics against M. abscessus Bamboo, with no observed antagonism^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

TBAJ-876 (1.6-25 mg/kg; oral gavage; once daily, 5 days per week; 4 weeks) demonstrates dose-dependent bactericidal activity against M. tuberculosis Beijing VN 2002-1585 in BALB/c mice, with the 25 mg/kg dose reducing median lung CFU counts by 6.6 log₁₀ over 4 weeks and rendering 2/5 animals culture negative^[1].
TBAJ-876 (10-30 mg/kg; p.o.; once daily; 10 consecutive days) reduces Mycobacterium abscessus bacterial loads in the lungs and spleen of infected NOD SCID mice, with efficacy comparable to bedaquiline at the 10 mg/kg dose^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

657.55

C₃₁H₃₇BrN₄O₇

2332841-25-3

Solid

White to off-white

COC1=NC(OC)=C(OC)C([C@H](C2=CC(C=C(Br)C=C3)=C3N=C2OC)[C@@](C4=CC(OC)=NC(OC)=C4)(O)CCN(C)C)=C1

Room temperature in continental US; may vary elsewhere.

• [1]. Mudde SE, et al. Relative Contributions of the Novel Diarylquinoline TBAJ-876 and its Active Metabolite to the Bactericidal Activity in a Murine Model of Tuberculosis. J Infect Dis. 2024;230(6):e1366-e1374.  [Content Brief]

  [2]. Sarathy JP, et al. TBAJ-876, a 3,5-Dialkoxypyridine Analogue of Bedaquiline, Is Active against Mycobacterium abscessus. Antimicrob Agents Chemother. 2020;64(4):e02404-19. Published 2020 Mar 24.  [Content Brief]