OSI-027 (ASP-4786, CERC-006, AEVI-006)

Description:OSI-027 (formerly known as ASP4786; AEVI006; CERC006) is a novel, potent, selective, orally bioavailable and ATP-competitive dual inhibitor of mTORC1 (mammalian target of rapamycin 1) and mTORC2 with potential anticancer activity. It inhibits mTORC1/2 with IC50 of 22 nM and 65 nM in cell-free assays, and showed more than 100-fold selectivity for mTOR over PI3Kalpha, PI3Kbeta, PI3Kgamma or DNA-PK. OSI-027 has potential antineoplastic activity and is being developed as an anticancer agent through inhibiting mTORC1 and mTORC2. In cellular assays, OSI-027 inhibits the phosphorylation of mTORC1 and mTORC2 substrates including AKT, PRAS40 and S6K1, which results in the blockade of downstream signaling. Dual inhibition of the mTOR kinase complexes mTORC1 and mTORC2 by OSI-27 decreases tumor xenograft growth in vivo and VEGF secretion in vitro.

References: Cancer Res. 2011 Mar 1; 71(5):1573-83; Clin Cancer Res. 2011 Jul 1; 17(13):4378-88; Breast Cancer Res Treat. 2012 Aug; 134(3):1057-66.

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