The β-ketoacyl-AcpM synthase (KasA) of Mycobacterium tuberculosis is an essential enzyme in the mycobacterial fatty acid biosynthesis (FAS-II) pathway and is thought to be a promising target for antibacterial discovery. The isolation of several natural product inhibitors of the KAS enzymes, including thiolactomycin (TLM), platensimycin and cerulenin has underscored the importance of KasA as an antibacterial drug target. This program seeks to identify and develop novel, small molecule inhibitors of KasA which can be used in combination with other agents to improve therapy and to treat drug-resistant forms of TB.