PHA-665752 is an oxindole-based, ATP-competitive c-Met and Ron inhibitor with IC50 potencies of 9 nM, and 68 nM, respectively. [1] It is >50-fold selective compared to a broad panel of both tyrosine and serine-threonine kinases. In cellular studies, PHA-665752 inhibits HGF-stimulated and constitutive c-Met phosphorylation as well as downstream signal transduction mediators such as Gab-1, Akt, phospholipase C gamma, and focal adhesion kinase. Inhibition of c-Met phosphorylation is dose-dependent and correlates well with tumor growth inhibition.
PHA-665752 induced apoptosis and cell cycle arrest in BaF3.TPR-MET cells at an IC50 of 60 nM. [2] Additionally, PHA-665752 has been suggested to inhibit lung tumorigenesis in mutant K-Ras mice and may be a formidable treatment for NSCLC. [3]
Technical information:
| Chemical Formula: | C32H34Cl2N4O4S | |
| CAS #: | 477575-56-7 | |
| Molecular Weight: | 641.61 | |
| Purity: | >98% | |
| Appearance: | Yellow | |
| Chemical Name: | (R,Z)-5-(2,6-dichlorobenzylsulfonyl)-3-((3,5-dimethyl-4-(2-(pyrrolidin-1-ylmethyl)pyrrolidine-1-carbonyl)-1H-pyrrol-2-yl)methylene)indolin-2-one | |
| Solubility: | Up to 100 mM in DMSO | |
| Synonyms: | PHA-665752, PHA 665752, PHA665752 |
Shipping Condition: The product is shipped in a glass vial at ambient temperature.
Storage condition: For longer shelf life, store solid powder at 4oC desiccated, or store DMSO solution at -20oC.
Reference:
| 1. | Christensen 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, 7345-7355. Pubmed ID: 14612533 |
| 2. | Ma et al., A selective small molecule c-MET Inhibitor, PHA665752, cooperates with rapamycin. Clin. Cancer Res. 2005, 11, 2312-2139 Pubmed ID: 15788682 |
| 3. | Yang et al., A selective small molecule inhibitor of c-Met, PHA-665752, reverses lung premalignancy induced by mutant K-ras. Mol. Cancer Ther. 2008, 7, 952-960. Pubmed ID: 18413809 |
Other Information:
Product Specification (pdf)
MSDS (pdf)
Certificate of Analysis is available upon request.
