API-1

Description: API-1 is a novel and potent Akt inhibitor, inducing GSK3-dependent, beta-TrCP- and FBXW7-mediated Mcl-1 degradation, resulting in induction of apoptosis . API-1 rapidly and potently reduced the levels of Mcl-1 primarily in API-1-senstive lung cancer cell lines. Ectopic expression of Mcl-1 protected cells from induction of apoptosis by API-1. API-1 treatment decreased the half-life of Mcl-1, whereas inhibition of the proteasome with MG132 rescued Mcl-1 reduction induced by API-1. API-1 decreased Mcl-1 levels accompanied with a rapid increase in Mcl-1 phosphorylation (S159/T163). Moreover, inhibition of GSK3 inhibited Mcl-1 phosphorylation and reduction induced by API-1 and antagonized the effect of API-1 on induction of apoptosis.

References: Ren H, Koo J, Guan B, Yue P, Deng X, Chen M, Khuri FR, Sun SY. The E3 ubiquitin ligases beta-TrCP and FBXW7 cooperatively mediates GSK3-dependent Mcl-1 degradation induced by the Akt inhibitor API-1, resulting in apoptosis. Mol Cancer. 2013 Nov 22; 12:146. doi: 10.1186/1476-4598-12-146. PubMed PMID: 24261825.