PHA-665752

• CAT Number: I003668
• CAS Number: 477575-56-7
• Molecular Formula: C32H34Cl2N4O4S
• Molecular Weight: 641.6
• Purity: ≥95%
• Target: c-MET
• Solubility: DMSO ≥125mg/mL Water <1.2mg/mL Ethanol ≥124mg/mL
• Storage: Sealed in dry,2-8°C
• IC50: 9 nM
• IUPAC Name: (3Z)-5-[(2,6-dichlorophenyl)methylsulfonyl]-3-[[3,5-dimethyl-4-[(2R)-2-(pyrrolidin-1-ylmethyl)pyrrolidine-1-carbonyl]-1H-pyrrol-2-yl]methylidene]-1H-indol-2-one
• InChI: InChI=1S/C32H34Cl2N4O4S/c1-19-29(35-20(2)30(19)32(40)38-14-6-7-21(38)17-37-12-3-4-13-37)16-24-23-15-22(10-11-28(23)36-31(24)39)43(41,42)18-25-26(33)8-5-9-27(25)34/h5,8-11,15-16,21,35H,3-4,6-7,12-14,17-18H2,1-2H3,(H,36,39)/b24-16-/t21-/m1/s1
• InChIKey: OYONTEXKYJZFHA-SSHUPFPWSA-N
• SMILES: O=C1/C(C2=CC(S(CC3=C(Cl)C=CC=C3Cl)(=O)=O)=CC=C2N1)=CC4=C(C)C(C(N5[C@@H](CN6CCCC6)CCC5)=O)=C(C)N4

PHA-665752（Cat No.:I003668） is a highly potent and selective inhibitor of the c-Met receptor tyrosine kinase. It works by competitively binding to the ATP-binding site of c-Met, thus preventing the phosphorylation of c-Met and downstream signaling pathways that promote cell proliferation, migration, and invasion. PHA-665752 has demonstrated antitumor activity in preclinical models of various cancers that are driven by c-Met dysregulation, including lung, gastric, and liver cancer.

Reference

1:Effects of PHA-665752 and cetuximab combination treatment on in vitro and murine xenograft growth of human colorectal cancer cells with KRAS or BRAF mutations. Jia YT, Yang DH, Zhao Z, Bi XH, Han WH, Feng B, Zhi J, Gu B, Duan Z, Wu JH, Ju YC, Wang MX, Li ZX.Curr Cancer Drug Targets. 2017 Mar 30. doi: 10.2174/1568009617666170330112841. [Epub ahead of print] PMID: 28359236 2:MET inhibitor PHA-665752 suppresses the hepatocyte growth factor-induced cell proliferation and radioresistance in nasopharyngeal carcinoma cells. Liu T, Li Q, Sun Q, Zhang Y, Yang H, Wang R, Chen L, Wang W.Biochem Biophys Res Commun. 2014 Jun 20;449(1):49-54. doi: 10.1016/j.bbrc.2014.04.147. Epub 2014 May 4. PMID: 24802404 3:Celastrol exerts synergistic effects with PHA-665752 and inhibits tumor growth of c-Met-deficient hepatocellular carcinoma in vivo. Jiang HL, Jin JZ, Wu D, Xu D, Lin GF, Yu H, Ma DY, Liang J.Mol Biol Rep. 2013 Jul;40(7):4203-9. doi: 10.1007/s11033-013-2501-y. Epub 2013 May 7. PMID: 23649759 4:A selective small molecule inhibitor of c-Met, PHA-665752, reverses lung premalignancy induced by mutant K-ras. Yang Y, Wislez M, Fujimoto N, Prudkin L, Izzo JG, Uno F, Ji L, Hanna AE, Langley RR, Liu D, Johnson FM, Wistuba I, Kurie JM.Mol Cancer Ther. 2008 Apr;7(4):952-60. doi: 10.1158/1535-7163.MCT-07-2045. PMID: 18413809 Free PMC Article5:Amplification of MET may identify a subset of cancers with extreme sensitivity to the selective tyrosine kinase inhibitor PHA-665752. Smolen GA, Sordella R, Muir B, Mohapatra G, Barmettler A, Archibald H, Kim WJ, Okimoto RA, Bell DW, Sgroi DC, Christensen JG, Settleman J, Haber DA.Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2316-21. Epub 2006 Feb 6. PMID: 16461907 Free PMC Article