H3B-120

H3B-120 is a selective, competitive, and allosteric small-molecule inhibitor of carbamoyl phosphate synthetase 1 (CPS1). Developed by H3 Biomedicine, H3B-120 binds to an allosteric pocket situated between the integrating and ATP A domains of CPS1, inducing a conformational change that blocks ATP binding and subsequent catalysis. CPS1 catalyzes the first step of the urea cycle, converting ammonia to carbamoyl phosphate. In certain cancers, such as MYC-driven medulloblastoma, LKB1-deficient non-small cell lung cancer (NSCLC), and other tumor types, CPS1 is overexpressed to support pyrimidine biosynthesis or prevent toxic ammonia accumulation. By inhibiting CPS1, H3B-120 impairs both the urea cycle and pyrimidine synthesis, demonstrating potential antitumor activity.

Other names

1,4-Piperidinedicarboxamide, N1-methyl-N4-(4-methyl-2-thiazolyl)-N1-(phenylmethyl)-N1-benzyl-N1-methyl-N4-(4-methylthiazol-2-yl)piperidine-1,4-dicarboxamide