S63845

S63845 is a potent and selective small molecule inhibitor of myeloid cell leukemia 1 (MCL1), a member of the BCL-2 family of anti-apoptotic proteins. It binds to the BH3-binding groove of human MCL1 with high affinity (Kd = 0.19 nM), disrupting its interaction with pro-apoptotic proteins BAK and BAX, thereby activating the mitochondrial apoptotic pathway in cancer cells[1][2][4]. Preclinical studies have shown that S63845 induces apoptosis selectively in MCL1-dependent cancer cells—including multiple myeloma, leukemia, and lymphoma—while sparing healthy hematopoietic stem cells[4][5]. The compound has demonstrated efficacy as a single agent and in combination with other anti-cancer drugs across various solid tumor-derived cell lines and hematologic malignancy models[4][9]. Developed initially by Vernalis (R&D) Ltd., it remains at the preclinical stage for indications such as metastatic castration-resistant prostate cancer and hematologic neoplasms[3].