Cat. No. Name Size Price Add Cart
KI1169PHA-6657525 mg$112
PHA-66575210 mg$192
PHA-66575250 mg$752
PHA-665752200 mg$2512

Chemical Characteristic

Product NamePHA-665752
CAS No.477575-56-7
Molecular Weight 641.61
FormulaC32H34Cl2N4O4S
Chemical 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
SmilesN1([C@H](CCC1)CN1CCCC1)C(=O)c1c([nH]c(c1C)/C=C/1\C(=O)Nc2c1cc(cc2)S(=O)(=O)Cc1c(cccc1Cl)Cl)C
Chemical Structure

Biological activities

PHA-665752 is a potent, ATP-competitive inhibitor of c-Met kinase with an IC50 of 9 nM and Ki value of 4 nM. PHA-665752 also exhibits >50-fold selectivity for c-Met compared with a panel of diverse tyrosine and serine-threonine kinases. In cellular studies, PHA-665752 potently inhibits c-Met RTK autophosphorylation in NIH3T3 cells engineered to express high levels of c-Met and HGF (S114 cells), HGF-stimulated A549 lung carcinoma cells, and mouse B16-F1 melanoma cells with IC50 values of 42, 25 and 50 nM, respectively. In GTL-16 cells, PHA-665752 (0.05-1.25 µM) completely inhibits growth in soft agar, inhibits cell proliferation, and induces apoptosis in both the presence and absence of HGF. In GTL-16 cells, PHA-665752 (100 nM) also potently inhibits constitutive signaling through ERK, Akt, FAK, PLC-γ , and STAT pathways. In S114 and GTL-16 xenografts models, PHA-665752 (25 mg/kg) inhibits c-Met phosphorylation for up to 12 hours and associates with dose-dependent tumor growth inhibition.[1] In NCI-H69 (small cell lung cancer) and NCI-H441 (non??mall cell lung cancer) xenografts model, PHA-665752 treatment (0.825 mg/kg/d) reduces tumorigenicity by 99% and 75%, respectively. PHA-665752 (0.825 mg/kg/d) also inhibits c-Met phosphorylation at the autophosphorylation and c-Cbl binding sites in mouse xenografts derived from non-small cell lung cancer cell lines (NCI-H441 and A549) and small cell lung cancer cell line (NCI-H69).[2]

Protocols

In vivo: PHA-665752 is dissolved in DMSO.[2]

References

[1] Christensen JG, et al. A selective small molecule inhibitor of c-Met kinase inhibits c-Met-dependent phenotypes in vitro and exhibits cytoreductive antitumor activity in vivo. Cancer Res. 2003, 63(21): 7345-7355.
[2] Puri N, et al. A selective small molecule inhibitor of c-Met, PHA665752, inhibits tumorigenicity and angiogenesis in mouse lung cancer xenografts. Cancer Res. 2007, 67(8): 3529-3534.

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