420089-51-6

Thiophene-2 (TP2) is a specific polyketide synthase 13 (Pks13) inhibitor. Thiophene-2 inhibits mycolic acid biosynthesis and rapidly leads to mycobacterial cell death. Thiophene-2 is active against Mycobacterium tuberculosis with a MIC value of 1 μM, and has potent anti-tuberculosis activity[1].

ChEBI: Thiophene-2 is an organosulfur heterocyclic compound.

Thiophene-2 (TP2) is an inhibitor of polyketide synthase 13 (Pks13)which plays a critical role in the biosynthesis of mycolic acidan essential component of the cell wall in M. tuberculosisand is a potential new target for tuberculosis treatment. TP2 inhibits FadD32-dependent loading of the mycolic acid precursor meromycoloyl chain onto acyl carrier protein (ACP) domains located at the N terminus of Pks13preventing synthesis of mycolic acid and resulting in mycobacterial cell death. TP2 bacteriosidal activity is equivalent to treatment with the first-line drug isoniazidand enhances its activitybut is less likely to cause resistance. The minimal inhibitory concentration (MIC) values of TP2 against drug-susceptible multidrug-resistant M. tuberculosis strains is approximately 1 μM.

[1] Regina Wilson, et al. Antituberculosis Thiophenes Define a Requirement for Pks13 in Mycolic Acid Biosynthesis. Nat Chem Biol. 2013 Aug;9(8):499-506. DOI:10.1038/nchembio.1277