TMU27a

TMU27a is a first-in-class, non-nucleoside small molecule inhibitor of ribonucleotide reductase (RNR) developed by Cleveland Clinic and Case Western Reserve University. Identified via an in silico screen for high-affinity binding to the catalytic site of RNR, TMU27a binds with a Kd of 150 nM. Unlike the nucleoside analog gemcitabine, TMU27a is designed to avoid off-target binding to other nucleotide-binding proteins such as DNA polymerase lambda, thereby minimizing dose-limiting toxicities like myelosuppression and hepatotoxicity. TMU27a reduces dATP pools, stalls replication forks, and induces S and G2/M-phase cell cycle arrest, leading to genomic instability, DNA damage, and apoptosis. It is currently in preclinical development for the treatment of triple-negative breast cancer (TNBC) and other aggressive solid tumors.

Other names

TMU