mTOR Inhibitor, WYE-132

• CAT Number: I000541
• CAS Number: 1144068-46-1
• Molecular Formula: C₂₇H₃₃N₇O
• Molecular Weight: 519.6
• Purity: ≥95%
• Target: mTOR
• Solubility: DMSO: ≥ 62 mg/mL
• Storage: -20°C Freezer
• IC50: 0.19 nM
• IUPAC Name: 1-[4-[1-(1,4-dioxaspiro[4.5]decan-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-methylurea
• InChI: 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)
• InChIKey: QLHHRYZMBGPBJG-UHFFFAOYSA-N
• SMILES: CNC(=O)NC1=CC=C(C=C1)C2=NC3=C(C=NN3C4CCC5(CC4)OCCO5)C(=N2)N6CC7CCC(C6)O7

WYE-125132 (Cat No.:I000541) is a highly potent, ATP-competitive mTOR inhibitor with IC50 of 0.19 nM; is more selective for mTOR than PI3Ks or PI3K-related kinases hSMG1 and ATR. If you need, please contact us in time, and we will reply as soon as possible within 24 hours.

Reference

1:Cancer Res. 2010 Jan 15;70(2):621-31. doi: 10.1158/0008-5472.CAN-09-2340. Epub 2010 Jan 12. Beyond rapalog therapy: preclinical pharmacology and antitumor activity of WYE-125132, an ATP-competitive and specific inhibitor of mTORC1 and mTORC2.Yu K,Shi C,Toral-Barza L,Lucas J,Shor B,Kim JE,Zhang WG,Mahoney R,Gaydos C,Tardio L,Kim SK,Conant R,Curran K,Kaplan J,Verheijen J,Ayral-Kaloustian S,Mansour TS,Abraham RT,Zask A,Gibbons JJ, PMID: 20068177 DOI: 10.1158/0008-5472.CAN-09-2340 Abstract: The mammalian target of rapamycin (mTOR) is a major component of the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway that is dysregulated in 50% of all human malignancies. Rapamycin and its analogues (rapalogs) partially inhibit mTOR through allosteric binding to mTOR complex 1 (mTORC1) but not mTOR complex 2 (mTORC2), an emerging player in cancer. Here, we report WYE-125132 (WYE-132), a highly potent, ATP-competitive, and specific mTOR kinase inhibitor (IC(50): 0.19 +/- 0.07 nmol/L; >5,000-fold selective versus PI3Ks). WYE-132 inhibited mTORC1 and mTORC2 in diverse cancer models in vitro and in vivo. Importantly, consistent with genetic ablation of mTORC2, WYE-132 targeted P-AKT(S473) and AKT function without significantly reducing the steady-state level of the PI3K/PDK1 activity biomarker P-AKT(T308), highlighting a prominent and direct regulation of AKT by mTORC2 in cancer cells. Compared with the rapalog temsirolimus/CCI-779, WYE-132 elicited a substantially stronger inhibition of cancer cell growth and survival, protein synthesis, cell size, bioenergetic metabolism, and adaptation to hypoxia. Oral administration of WYE-132 to tumor-bearing mice showed potent single-agent antitumor activity against MDA361 breast, U87MG glioma, A549 and H1975 lung, as well as A498 and 786-O renal tumors. An optimal dose of WYE-132 achieved a substantial regression of MDA361 and A549 large tumors and caused complete regression of A498 large tumors when coadministered with bevacizumab. Our results further validate mTOR as a critical driver for tumor growth, establish WYE-132 as a potent and profound anticancer agent, and provide a strong rationale for clinical development of specific mTOR kinase inhibitors as new cancer therapy.