OSI-027

OSI‑027 is an orally bioavailable small molecule that acts as a selective and potent dual inhibitor of the mammalian target of rapamycin complexes mTORC1 and mTORC2. It inhibits mTOR kinase activity with IC50 values of 22 nM (mTORC1) and 65 nM (mTORC2), showing over 100-fold selectivity for mTOR compared to related kinases such as PI3Kα/β/γ or DNA-PK[1][8]. By inhibiting both complexes, OSI‑027 blocks phosphorylation of downstream effectors including AKT (a substrate of mTORC2), S6K1 and 4E-BP1 (substrates of mTORC1), leading to cell cycle arrest in G0/G1 phase and suppression of cancer cell proliferation[5][6][8]. Preclinical studies have demonstrated antitumor activity in various cancer models including pancreatic ductal adenocarcinoma, colon cancer, cholangiocarcinoma, lymphoma, and other solid tumors[3][4][5][6]. The drug has been evaluated in early-phase clinical trials for advanced solid tumors and lymphomas. Renal function disturbances have been noted as a significant side effect[4].

Other names

CYCLOHEXANECARBOXYLIC ACID, 4-(4-AMINO-5-(7-METHOXY-1H-INDOL-2-YL)IMIDAZO(5,1-F)(1,2,4)TRIAZIN-7-YL)-, TRANS-