Comparison

PHA-665752 European Partner

Item no. S1070-10
Manufacturer Selleckchem
CASRN 477575-56-7
Amount 10 mg
Category
Type Inhibitors
Specific against other
ECLASS 10.1 32160490
ECLASS 11.0 32160490
UNSPSC 12000000
Alias 477575-56-7'
Similar products PHA-665752
Available
Administration
Injection via bolus i.v.
Animal Models
Female athymic mice (nu/nu) bearing S114 or GTL-16 tumor xenografts
Cell lines
S114, GTL-16, NCI-H441, and BxPC-3
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
Concentrations
Dissolved in DMSO, final concentrations ca.10 uM
Description
PHA-665752 is a potent, selective and ATP-competitive c-Met inhibitor with IC50 of 9 nM.
Dosages
ca.30 mg/kg/day
Formulation
Formulated in vehicle (L-lactate (pH 4.8) and 10% polyethylene glycol)
IC50
9 nM [1], 9 nM [1], 9 nM [1], 9 nM [1], 9 nM [1], 9 nM [1]
In vitro
PHA-665752 significantly inhibits c-Met kinase activity with Ki of 4 nM, and exhibits >50-fold selectivity for c-Met compared with various tyrosine and serine-threonine kinases. PHA-665752 potently inhibits the HGF-stimulated c-Met autophosphorylation with IC50 of 25-50 nM. PHA-665752 also significantly blocks HGF- and c-Met-dependent functions such as cell motility and cell proliferation with IC50 of 40-50 nM and 18-42 nM, respectively. In addition, PHA-665752 potently inhibits HGF-stimulated or constitutive phosphorylation of mediators of downstream of c-Met such as Gab-1, ERK, Akt, STAT3, PLC-gamma, and FAK in multiple tumor cell lines. [1] PHA-665752 inhibits cell growth in TPR-MET-transformed BaF3 cells with IC50 of <60 nM, and inhibits constitutive cell motility and migration by 92.5% at 0.2 uM. Inhibition of c-Met by PHA665752 (0.2 uM) also induces cell apoptosis of 33.1% and G1 cell cycle arrest with cells in G1 phase increasing from 42.4% to 77.0%. PHA665752 can cooperate with rapamycin to inhibit cell growth of TPR-MET-transformed BaF3 cells and non-small cell lung cancer H441 cells. [2]
In vivo
Administration of PHA-665752 induces a dose-dependent tumor growth inhibition of S114 xenografts by 20 %, 39% and 68%, at dose of 7.5, 15, and 30 mg/kg/day, respectively. [1] PHA665752 treatment significantly reduces the tumor growth of NCI-H69, NCI-H441 and A549 in mouse xenografts by 99%, 75%, and 59%, respectively. PHA665752 also significantly inhibits angiogenesis by >85%, due to decreasing the production of vascular endothelial growth factor and increasing the production of the angiogenesis inhibitor thrombospondin-1. [3]
Incubation Time
18, or 72 hours
Kinase Assay
In vitro enzyme assay, The c-Met kinase domain GST-fusion protein is used for the c-Met assay. The IC50 value of PHA-665752 for the inhibition of c-Met is based on phosphorylation of kinase peptide substrates or poly-glu-tyr in the presence of ATP and divalent cation (MgCl2 or MnCl2 10-20 mM). The linear range (i.e., the time period over which the rate remains equivalent to the initial rate) is determined for c-Met, and the kinetic measurement and IC50 determination are performed within this range.
Method
For proliferation assays, cells are grown in medium with 0.1% FBS for 48 hours after which they are treated with various concentrations of PHA-665752 in HGF (50 ng/mL) in a medium containing 2% FBS. After 18 hours, cells are incubated with BrdUrd for 1 hour, fixed, and stained with anti-BrdUrd peroxidase-conjugated antibody, and plates are read at 630 nm. For apoptosis assays, cells are grown in medium with 2% FBS in presence and absence of HGF (50 ng/mL) and various concentrations of PHA-665752 for 72 hours. After 72 hours, a mixture containing ethidium bromide and acridine orange is added, and apoptotic cells (bright orange cells or cell fragments) are counted by fluorescence microscopy.
Molecular Weight (MW)
641, 61
Picture ChemicalStructure Description
PHA-665752 Chemical Structure
Picture Description 1
Data independently produced by, , , Dr. Zhang, of Tianjin Medical University, PHA-665752purchased from Selleck, Western blot analysis of p-c-Met and c-Met. 0-100M PHA665752 was added.
Solubility (25C)
DMSO 128 mg/mL, Water <1 mg/mL, Ethanol <1 mg/mL
Storage
2 years -20CPowder, 2 weeks4Cin DMSO, 2 months-80Cin DMSO

Note: The presented information and documents (Manual, Product Datasheet, Safety Datasheet and Certificate of Analysis) correspond to our latest update and should serve for orientational purpose only. We do not guarantee the topicality. We would kindly ask you to make a request for specific requirements, if necessary.

All products are intended for research use only (RUO). Not for human, veterinary or therapeutic use.

Amount: 10 mg
Available: In stock
available

Compare

Add to wishlist

Get an offer

Request delivery time

Ask a technical question

Submit a bulk request

Questions about this Product?
 
Close