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The ClpP1P2 inhibitor program is a preclinical drug discovery initiative by the Global Alliance for TB Drug Development (TB Alliance) focused on developing small molecule inhibitors of the Caseinolytic protease P1/P2 (ClpP1P2) complex. ClpP1P2 is an essential, ATP-dependent serine protease in *Mycobacterium tuberculosis* that plays a critical role in protein degradation and the maintenance of cellular proteostasis. Inhibition of this enzyme complex leads to the toxic accumulation of misfolded proteins, resulting in bacterial cell death. This mechanism is distinct from existing TB therapies, potentially offering a new tool against drug-resistant strains. The program is currently in the lead optimization stage of preclinical development.
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