SKI-178

Description: SKI-178 is a sphingosine kinase 1 (SphK1) inhibitor with IC50 of 0.1-1.8 µM. It induces prolonged mitosis followed by apoptotic cell death through the intrinsic apoptotic cascade. The sustained activation of CDK1 during prolonged mitosis, mediated by SKI-178 leads to the simultaneous phosphorylation of the prosurvival Bcl-2 family members, Bcl-2 and Bcl-xl, as well as the phosphorylation and subsequent degradation of Mcl-1. Target: Apoptosis, S1P Receptor. Smiles: COc1ccc(cc1)-c1cc([nH]n1)C(=O)N\N=C(/C)c1ccc(OC)c(OC)c1. References: Hengst JA, et al. SKI-178: A Multitargeted Inhibitor of Sphingosine Kinase and Microtubule Dynamics Demonstrating Therapeutic Efficacy in Acute Myeloid Leukemia Models. Cancer Transl Med. 2017,3(4):109-121.