The mammalian target of rapamycin (mTOR) is a serine-threonine kinase that is central to two protein complexes, mTORC1 and mTORC2. These complexes are differentially regulated (e.g., only mTORC1 is sensitive to rapamycin ) and regulate different pathways. OSI-027 is an inhibitor of the catalytic site of mTOR and, as a result, inhibits both mTORC1 and mTORC2 (IC50s = 22 and 65 nM, respectively). It is selective for mTOR over phosphatidylinositol 3-kinase isoforms and DNA protein kinase. OSI-027 prohibits proliferation, induces autophagy, and potentiates apoptosis in BCR-ABL transformed cells and other cancer cells at 10 μM. OSI-027 is effective in vivo, blocking the phosphorylation of targets of mTORC1 and mTORC2 and suppressing tumor growth in several different human xenograft models.
OSI-027 is a kinase inhibitor with anti-tumor activity, used in treatment of breast cancer.
ChEBI: 4-[4-amino-5-(7-methoxy-2-indolylidene)-1H-imidazo[5,1-f][1,2,4]triazin-7-yl]-1-cyclohexanecarboxylic acid is a member of indoles.
[1] bhagwat s v, gokhale p c, crew a p, et al. preclinical characterization of osi-027, a potent and selective inhibitor of mtorc1 and mtorc2: distinct from rapamycin. molecular cancer therapeutics, 2011, 10(8): 1394-1406.
