OSI-027

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 (Cay-13346)) 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.Formal Name: trans-4-[4-amino-5-(7-methoxy-1H-indol-2-yl)imidazo[5,1-f][1,2,4]triazin-7-yl]-cyclohexanecarboxylic acid. CAS Number: 936890-98-1. Molecular Formula: C21H22N6O3. Formula Weight: 406.4. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 10 mg/ml, DMSO: 10 mg/ml, DMSO:PBS (pH 7.2) (1:1): 0.5 mg/ml, Ethanol: 0.1 mg/ml. lambdamax: 216, 294, 347 nm. SMILES: NC1=NC=NN2C1=C(C3=CC4=C(C(OC)=CC=C4)N3)N=C2[C@@H]5CC[C@@H](C(O)=O)CC5. InChi Code: InChI=1S/C21H22N6O3/c1-30-15-4-2-3-13-9-14(25-16(13)15)17-18-19(22)23-10-24-27(18)20(26-17)11-5-7-12(8-6-11)21(28)29/h2-4,9-12,25H,5-8H2,1H3,(H,28,29)(H2,22,23,24)/t11-,12-. InChi Key: JROFGZPOBKIAEW-HAQNSBGRSA-N.