SU9516

SU9516 is a synthetic small molecule belonging to the class of 3-substituted indolinones. It acts as a potent and selective inhibitor of cyclin-dependent kinases (CDKs), particularly CDK2, CDK1, and CDK5. The compound competitively inhibits ATP binding to CDK2/cyclin A with high potency (Ki ~0.031 μM) and also inhibits CDK1/cyclin B1 and CDK4/cyclin D1 at lower potencies. In cellular models, SU9516 induces apoptosis in tumor cells by inhibiting phosphorylation of the carboxyl-terminal domain (CTD) of RNA polymerase II on serine 2, leading to downregulation of antiapoptotic protein Mcl-1 at both mRNA and protein levels via proteasomal degradation pathways. This results in mitochondrial injury and cell death through increased oxidative stress. Additionally, it has been shown to enhance sensitivity to methotrexate in leukemia cells by downregulating dihydrofolate reductase (DHFR). The drug is experimental with no approved clinical indications[1][2][3][4][5][6].

Other names

3-[1-(3H-imidazol-4-yl)-meth-(Z)-ylidene]-5-methoxy-1,3-dihydro-indol-2-one