OPC-167832 is a potent and orally active dprE1 Inhibitor with an IC50 of 0.258 μM. OPC-167832 has antituberculosis activity and can be used for the research of tuberculosis caused by Mycobacterium tuberculosis[1]. OPC-167832 exhibits very low MICs against laboratory strains of M. tuberculosisH37Rv (MIC: 0.0005 μg ml) and Kurono (MIC: 0.0005 μg ml) and strains with monoresistance to rifampin (RIF), isoniazid (INH), ethambutol (EMB), streptomycin (STR), and pyrazinamide (PZA) (MIC: 0.00024-0.001 μg ml). However, OPC-167832 has minimal or no activity against standard strains of nonmycobacterial aerobic and anaerobic bacteria[1].The IC90 values of OPC-167832 against intracellular M. tuberculosis strains H37Rv and Kurono are 0.0048 and 0.0027 μg ml, respectively. OPC-167832 shows bactericidal activity against intracellular M. tuberculosis at a low concentration, and the bactericidal activity is saturated at concentrations of 0.004 μg ml or higher[1]. OPC-167832 (oral administration; 0.625-10 mg kg) exhibits a good pharmacokinetic characteristic. The plasma reaches peak at 0.5 h to 1.0 h (tmax) and is eliminated with a half-life (t1 2) of 1.3 h to 2.1 h OPC-167832 distribution in the lungs is approximately 2 times higher than that in plasma, and the Cmax and AUCt of OPC-167832 in plasma and the lungs shows dose dependency[1].OPC-167832 (oral administration; 0.625-10 mg kg; 4 weeks) significantly reduces lung CFU compared to the vehicle group. The dose-dependent decrease of lung CFU is observed from 0.625 mg kg to 2.5 mg kg. In a M. tuberculosis Kurono-infected ICR female mice model. OPC-167832 combines with DMD, BDQ, or LVX via oral gavage exhibits significantly higher efficacies than each single agent alone[1].[1].OPC-167832 (oral gavage; 2.5 mg kg; combination with DCMB; 12 weeks) demonstrates the most potent efficacy when compares with DC, DCB. The lung CFU count after 6 weeks of treatment is below the detection limit, and at the end of just 8 weeks of treatment, the bacteria in the lungs of all the evaluated mice had already been eradicate[1]. [1]. Norimitsu Hariguchi, et al. OPC-167832, a Novel Carbostyril Derivative with Potent Antituberculosis Activity as a DprE1 Inhibitor.Antimicrob Agents Chemother. 2020 May 21;64(6):e02020-19.
Polyketide synthase 13-IN-3 (compound 41) is a potent inhibitor of polyketide synthase 13, demonstrating a minimum inhibitory concentration (MIC) range of 0.0625-0.125 μg mL against the M. tuberculosis strain H37Rv.
Antibacterial agent 118 (also known as compound 20) is a potent antimycobacterial compound with activity against various mycobacterial strains, including Mtb H37Ra, M. aurum, M. smegmatis, Mtb H37Rv, and M. avium. The minimum inhibitory concentration (MIC) values for Antibacterial agent 118 against these strains are 40.7 μM, 10.2 μM, 163.0 μM, 62.5 μM, and 62.5 μM, respectively. This compound holds potential for tuberculosis research [1].
Antitubercular agent-16 (Compound 5q) is a potent antitubercular agent exhibiting high efficacy against various strains of M. tuberculosis, including H37Rv, CF16, CF61, CF76, CF152, and CF161, with MIC 90 values ranging from 0.40 to 23.51 μg mL. Notably, Antitubercular agent-16 demonstrates minimal cytotoxicity towards macrophages and pulmonary fibroblasts, further highlighting its potential as a therapeutic agent [1].
PknB-IN-1 (Compound 2) is an inhibitor of protein kinase B (PknB) with a concentration causing 50% inhibition (IC50) of 14.4 μM. This compound demonstrates anti-mycobacterial activity by effectively suppressing the growth of M. tuberculosisH37Rv strain, with a minimum inhibitory concentration (MIC) of 6.2 μg mL [1].