WYE-125132

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. WYE-125132 is an ATP-competitive inhibitor of mTOR (IC50 = 0.19 nM) that inhibits signaling through both mTORC1 and mTORC2. It is selective for mTOR over phosphatidylinositol 3-kinase isoforms. WYE-125132 is effective against mTORC1 and mTORC2 in diverse cancer models, both in vitro and in vivo. Oral administration of WYE-125132 alone blocks mTOR signaling and prevents tumor growth in breast, lung, renal, and glioma cancer xenografts in mice, while combination therapy with the VEGF-inhibitor bevacizumab causes complete regression of A498 renal carcinoma tumors. In addition to its applications in cancer, WYE-125132 has been used to delineate novel aspects of mTOR signaling.Formal Name: N-[4-[1-(1,4-dioxaspiro[4.5]dec-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-N'-methyl-urea. CAS Number: 1144068-46-1. Synonyms: WYE-132. Molecular Formula: C27H33N7O4. Formula Weight: 519.6. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 50 mg/ml, DMF:PBS(pH 7.2)(1:1): 0.5 mg/ml, DMSO: 30 mg/ml, Ethanol: 0.4 mg/ml. lambdamax: 203, 290 nm. SMILES: O=C(NC)NC(C=C1)=CC=C1C2=NC(N3CC4CCC(O4)C3)=C5C(N(C6CCC7(OCCO7)CC6)N=C5)=N2. InChi Code: InChI=1S/C27H33N7O4/c1-28-26(35)30-18-4-2-17(3-5-18)23-31-24(33-15-20-6-7-21(16-33)38-20)22-14-29-34(25(22)32-23)19-8-10-27(11-9-19)36-12-13-37-27/h2-5,14,19-21H,6-13,15-16H2,1H3,(H2,28,30,35). InChi Key: QLHHRYZMBGPBJG-UHFFFAOYSA-N.