Biochem/physiol Actions

Primary TargetInhA

General description

A cell-permeable, orally available, highly lipophilic 4-hydroxy-2-pyridone derivative that directly binds to the enoyl-substrate binding pocket of Mycobaterial enoyl reductase inhA in an NADH-dependent manner and inhibits its activity (IC₅₀ = 570 nM). Shown to be about 5 to 8 times more potent ((MIC₅₀ = 40 to 160 nM in multi-drug resistant strains of Mycobacterium) than isoniazid (MIC₅₀ = 330 nM) and PA-824 (MIC₅₀ = 400 nM). Exhibits in vivo efficacy in acute and established mouse models of Mycobacterium tuberculosis infection. Exhibits low to moderate metabolic clearance in mouse and human hepatic microsomes. Suggested to inhibit the fatty acid elongation step that blocks the biosynthesis of mycolic acids and weakens the cell wall mycolyl-arabinogalactan-peptidoglycan complex, and ultimately lysis of Mycobacterium.Please note that the molecular weight for this compound is batch-specific due to variable water content. Please refer to the vial label or the certificate of analysis for the batch-specific molecular weight. The molecular weight provided represents the baseline molecular weight without water.

A cell-permeable, orally available, highly lipophilic 4-hydroxy-2-pyridone derivative that directly binds to the enoyl-substrate binding pocket of Mycobaterial enoyl reductase inhA in an NADH-dependent manner and inhibits its activity (IC₅₀ = 570 nM). Shown to be about 5 to 8 times more potent ((MIC₅₀ = 40 to 160 nM in multi-drug resistant strains of Mycobacterium) than isoniazid (MIC₅₀ = 330 nM) and PA-824 (MIC₅₀ = 400 nM). Exhibits in vivo efficacy in acute and established mouse models of Mycobacterium tuberculosis infection. Exhibits low to moderate metabolic clearance in mouse and human hepatic microsomes. Suggested to inhibit the fatty acid elongation step that blocks the biosynthesis of mycolic acids and weakens the cell wall mycolyl-arabinogalactan-peptidoglycan complex, and ultimately lysis of Mycobacterium.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Other Notes

Manjunatha, U., et al. 2015. Sci. Trans. Med.7, 269.

Packaging

25 mg in Glass bottle

Packaged under inert gas

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Warning

Toxicity: Regulatory Review (Z)