MTB-9655

MTB-9655 is a first-in-class, orally bioavailable, potent, and selective small molecule inhibitor of acetyl-Coenzyme A synthetase short chain family member 2 (ACSS2). ACSS2 catalyzes the conversion of acetate and Co-enzyme A to acetyl-CoA, a key metabolite in cellular metabolism. In certain cancers—including breast, colorectal, ovarian, and lung—ACSS2 expression is upregulated or amplified. By inhibiting ACSS2 (IC50 = 0.15 nM in biochemical assays; EC50 = 3 nM in cellular assays), MTB-9655 disrupts tumor cell metabolism and has demonstrated anti-tumor effects in xenograft models expressing high levels of ACSS2. The drug is currently being evaluated in Phase 1 clinical trials for advanced solid tumors that have failed standard therapies[1][4][6][9]. It also exhibits off-target inhibition of UGT1A1 at higher concentrations[1].