PHA-665752 is a small-molecule inhibitor of c-Met, inhibits tumorigenicity and angiogenesis in mouse lung cancer xenografts. c-Met is a tyrosine kinase receptor for hepatocyte growth factor/scatter factor (HGF/SF). PHA665752 inhibited specific phosphorylation of TPR-MET as well as phosphorylation of downstream targets of the mammalian target of rapamycin pathway. Short-term treatment with PHA-665752 decreased the numbers of premalignant lung lesions and induced apoptosis in tumor cells and vascular endothelial cells within lesions. In cell culture, PHA-665752 induced apoptosis of a lung adenocarcinoma cell line derived from Kras(LA1) mice (LKR-13) and a murine lung endothelial cell line (MEC). PHA665752 was shown to inhibit cMet/HGF/SF signaling in vitro, suggesting c-Met inhibitors may have efficacy for blocking local progression and/or metastatic spread of c-Met-positive NBL in vivo.
|Source||Biochem Biophys Res Commun (2014). Figure 2.PHA-665752|
|Cell Lines||CNE-1 and HONE-1 cells|
|Incubation Time||72 h|
|Results||Further experiments showed that PHA-665752 inhibited cell proliferation in a dose-dependent manner in the CNE-1 and HONE-1 cells|
|Cell lines||S114, GTL-16, NCI-H441, or BxPC-3 cells|
|Preparation method||Cell Proliferation Assays. S114, GTL-16, NCI-H441, or BxPC-3 cells were seeded in 96-well plates at 9000 cells/well in medium with 10% FBS. After incubation for 48 h in low serum (0.5% FBS, S114; 0.1% FBS, GTL-16, NCI-H441, and BxPC-3), cells were treated with different concentrations of PHA-665752 for 18 h at 37°C. HGF (50 ng/ml) was added for 18 h before BrdUrd for studies involving GTL-16, H441, and BxPC-3. After incubation with BrdUrd labeling reagent for 1 h (Sigma Biochemicals, St. Louis, MO), cells were fixed and BrdUrd incorporation into newly synthesized DNA was assessed using anti-BrdUrd peroxidase-conjugated antibody followed by colorimetric determination at 630 nm.|
|Animal models||athymic mice bearing S114 or GTL-16 tumor xenografts|
|Formulation||L-lactate (pH 4.8) and 10% polyethylene glycol|
|Dosages||7.5, 15, 30 mg/kg/day|
|Administration||i.v. bolus via tail vein injection|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||DMSO 100 mg/mL|
PHA665752, a small-molecule inhibitor of c-Met, inhibits hepatocyte growth factor-stimulated migration and proliferation of c-Met-positive neuroblastoma cells.
Crosswell HE, et al. BMC Cancer. 2009 Nov 25;9:411. PMID: 19939254.
A selective small molecule inhibitor of c-Met, PHA-665752, reverses lung premalignancy induced by mutant K-ras.
Yang Y, et al. Mol Cancer Ther. 2008 Apr;7(4):952-60. PMID: 18413809.
|Related c-Met Products|
CEP-40783 (RXDX-106) is a potent, selective and orally available inhibitor of AXL and c-Met with IC50 values of 7 nM and 12 nM, respectively.
Savolitinib (volitinib, AZD6094, HMPL-504) is a novel, potent, and selective MET inhibitor currently in clinical development in various indications, including PRCC. The IC50 values of this compound for c-Met and p-Met are 5 nM and 3 nM, respectively. It shows exquisite selectivity for c-Met over 274 kinase.
AMG 337 is an oral, small molecule, ATP-competitive, highly selective inhibitor of the MET receptor.
S49076 is a novel, potent inhibitor of MET, AXL/MER, and FGFR1/2/3 with IC50 values below 20 nmol/L.
Altiratinib(DCC-2701) is a novel c-MET/TIE-2/VEGFR inhibitor; effectively reduce tumor burden in vivo and block c-MET pTyr(1349)-mediated signaling, cell growth and migration as compared with a HGF antagonist in vitro.
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2017 AbMole BioScience. All Rights Reserved.