| Description |
MmpL3-IN-1 (compound 32) is a potent Mycobacterial membrane protein large 3 (MmpL3) inhibitor. MmpL3-IN-1 has anti-tuberculosis activity with the MIC<0.016 μg/mL in M. tuberculosis and can be used in studies of drug-resistant tuberculosis[1].
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| Related Catalog |
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| In Vitro |
MmpL3-IN-1 (compound 32) (0.26-64 μg/mL, 2-7days) has potent anti-M. tuberculosis activity with the MIC value of less than 0.016 μg/mL and with almost non-toxic to Vero cells[1]. MmpL3-IN-1 has good microsomal stability and little inhibition of hERG K+ channels with the IC50 value of more than 30 μM[1]. MmpL3-IN-1 (0.0625-1 μg/mL, 16 h) can inhibit TMM transport by targeting MmpL3, thereby affecting the formation of the cell wall of M. tuberculosis[1]. Cell Viability Assay[1] Cell Line: Vero cells Concentration: 0.26-64 μg/mL Incubation Time: 48 hours Result: Inhibited cell viability with an IC50 value of 35.3 μg/mL. Western Blot Analysis[1] Cell Line: M. tuberculosisH37Rv mc26206 Concentration: 0.0625-1 μg/mL Incubation Time: 16 hours Result: Resulted in the accumulation of alginate monomycin (TMM) expression and reduced cell wall-bound mycolic acid methyl esters (MAMEs) in a dose-dependent manner. Reduced synthesis of alginate dimycolate (TDM), together with accumulation of free mycolate at high concentration.
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| In Vivo |
MmpL3-IN-1 (compound 32) (oral gavage, 100 mg/kg, 5 days per week, 30 days) has effective anti-tuberculosis activity in SPF BALB/c female mice with H37Rv[1]. Animal Model: SPF BALB/c female mice with H37Rv[1] Dosage: 100 mg/kg Administration: Oral gavage; 5 days per week; 30 days Result: Showed a 2.0 log CFU reduction of H37Rv in lung colony forming units. Animal Model: BALB/c mouse (female) weighing 20-25 g[1] Dosage: Administration: 100 mg/kg p.o. or 10 mg/kg i.v. ; 0-24 hours Result: b>The pharmacokinetic parameters of MmpL3-IN-1 (compound 32) Parameter iv, 10 mg/kg po, 100 mg/kg t1/2(h) 7.37 7.48 Cmax (ng/mL) 5105 211 Tmax(h) 0.03 0.5 AUC0-t(h•ng/mL) 2475 1625 MRT0-t(h•ng/mL) 2.00 8.69 V (mL/kg) 42067 - CL (mL/h/kg) 3958 - F% - 6.6
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| References |
[1]. Hongyi Zhao, et al. Design, Synthesis, and Biological Evaluation of Pyrrole-2-carboxamide Derivatives as Mycobacterial Membrane Protein Large 3 Inhibitors for Treating Drug-Resistant Tuberculosis. J Med Chem. 2022 Aug 1.
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