NMS-1116354

NMS-1116354 is an orally bioavailable small molecule inhibitor of cell division cycle 7 (CDC7) kinase, developed by Nerviano Medical Sciences for the treatment of cancer, particularly advanced or metastatic solid tumors. The drug competitively inhibits the ATP-binding site of CDC7 kinase, a serine-threonine kinase essential for initiating DNA replication by phosphorylating minichromosome maintenance complex component 2 (MCM2). Inhibition of CDC7 leads to blockade of DNA replication and mitosis, induction of tumor cell apoptosis, and suppression of tumor proliferation in cells overexpressing CDC7. NMS-1116354 also exhibits inhibitory activity against cyclin-dependent kinase 9 (CDK9), which may contribute to its antitumor effects through additional pathways such as inhibition of transcriptional regulation. Preclinical studies have shown efficacy in colon cancer models and other solid tumors. Clinical development reached phase I trials in patients with advanced solid tumors but was discontinued.

Brand names

vulcanchem

Other names

PHA-00767491 hydrochloridePHA00767491 hydrochloridePHA 00767491 hydrochloride1,5,6,7-Tetrahydro-2-(4-pyridinyl)-4H-pyrrolo[3,2-c]pyridin-4-one hydrochloride