Home Protein Tyrosine Kinase c-Met inhibitor PHA-665752 For research use only.

PHA-665752

PHA-665752 is a potent, selective and ATP-competitive c-Met inhibitor with IC50 of 9 nM in cell-free assays, >50-fold selectivity for c-Met than RTKs or STKs.

PHA-665752 Chemical Structure

PHA-665752 Chemical Structure

CAS No. 477575-56-7

Purity & Quality Control

PHA-665752 Related Products

Signaling Pathway

c-Met Signaling Pathways

c-Met Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
NCI-SNU-5 Growth Inhibition Assay IC50=0.12375 μM SANGER
LB2241-RCC Growth Inhibition Assay IC50=0.15702 μM SANGER
KINGS-1 Growth Inhibition Assay IC50=0.35911 μM SANGER
ALL-PO Growth Inhibition Assay IC50=0.81277 μM SANGER
SK-LMS-1 Growth Inhibition Assay IC50=0.89846 μM SANGER
MV-4-11 Growth Inhibition Assay IC50=1.2947 μM SANGER
SUP-T1 Growth Inhibition Assay IC50=2.13964 μM SANGER
MRK-nu-1 Growth Inhibition Assay IC50=2.40056 μM SANGER
ES1 Growth Inhibition Assay IC50=3.34866 μM SANGER
NOS-1 Growth Inhibition Assay IC50=4.39867 μM SANGER
KM12 Growth Inhibition Assay IC50=4.418 μM SANGER
Becker Growth Inhibition Assay IC50=5.2466 μM SANGER
NCI-SNU-1 Growth Inhibition Assay IC50=5.63733 μM SANGER
EW-22 Growth Inhibition Assay IC50=7.73614 μM SANGER
ES6 Growth Inhibition Assay IC50=7.8195 μM SANGER
A498 Growth Inhibition Assay IC50=8.28446 μM SANGER
EW-16 Growth Inhibition Assay IC50=9.6543 μM SANGER
CTV-1 Growth Inhibition Assay IC50=9.85024 μM SANGER
ETK-1 Growth Inhibition Assay IC50=10.2931 μM SANGER
NCI-H1395 Growth Inhibition Assay IC50=10.8024 μM SANGER
DOHH-2 Growth Inhibition Assay IC50=10.9264 μM SANGER
GI-1 Growth Inhibition Assay IC50=11.8596 μM SANGER
HT-144 Growth Inhibition Assay IC50=14.2163 μM SANGER
ES5 Growth Inhibition Assay IC50=14.467 μM SANGER
NALM-6 Growth Inhibition Assay IC50=15.2196 μM SANGER
KNS-81-FD Growth Inhibition Assay IC50=15.5849 μM SANGER
TE-15 Growth Inhibition Assay IC50=16.5771 μM SANGER
SCC-15 Growth Inhibition Assay IC50=18.3498 μM SANGER
EoL-1-cell Growth Inhibition Assay IC50=18.4545 μM SANGER
NCI-H720 Growth Inhibition Assay IC50=18.771 μM SANGER
NB14 Growth Inhibition Assay IC50=19.5425 μM SANGER
KE-37 Growth Inhibition Assay IC50=19.8233 μM SANGER
LXF-289 Growth Inhibition Assay IC50=19.8629 μM SANGER
RPMI-8402 Growth Inhibition Assay IC50=20.3269 μM SANGER
SK-N-DZ Growth Inhibition Assay IC50=21.2131 μM SANGER
ACN Growth Inhibition Assay IC50=22.2497 μM SANGER
TE-11 Growth Inhibition Assay IC50=26.069 μM SANGER
COLO-800 Growth Inhibition Assay IC50=27.17 μM SANGER
MOLT-13 Growth Inhibition Assay IC50=27.1847 μM SANGER
697 Growth Inhibition Assay IC50=28.7633 μM SANGER
VA-ES-BJ Growth Inhibition Assay IC50=29.3729 μM SANGER
EW-13 Growth Inhibition Assay IC50=29.5045 μM SANGER
NB7 Growth Inhibition Assay IC50=32.2665 μM SANGER
MONO-MAC-6 Growth Inhibition Assay IC50=32.8795 μM SANGER
SW962 Growth Inhibition Assay IC50=33.4513 μM SANGER
KS-1 Growth Inhibition Assay IC50=33.9481 μM SANGER
KU812 Growth Inhibition Assay IC50=34.5702 μM SANGER
IMR-5 Growth Inhibition Assay IC50=37.4318 μM SANGER
BC-1 Growth Inhibition Assay IC50=38.033 μM SANGER
NCI-H510A Growth Inhibition Assay IC50=38.2032 μM SANGER
EW-18 Growth Inhibition Assay IC50=40.8303 μM SANGER
CCRF-CEM Growth Inhibition Assay IC50=42.2797 μM SANGER
HH Growth Inhibition Assay IC50=43.5069 μM SANGER
NCI-H2171 Growth Inhibition Assay IC50=46.0272 μM SANGER
LC-2-ad Growth Inhibition Assay IC50=49.1413 μM SANGER
Click to View More Cell Line Experimental Data

Biological Activity

Description PHA-665752 is a potent, selective and ATP-competitive c-Met inhibitor with IC50 of 9 nM in cell-free assays, >50-fold selectivity for c-Met than RTKs or STKs.
Targets
c-Met [1]
(Cell-free assay)		 RON [1]
(Cell-free assay)		 Flk1 [1]
(Cell-free assay)
9 nM 68 nM 200 nM
In vitro
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-γ, 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 μM. Inhibition of c-Met by PHA665752 (0.2 μM) 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]
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.
Cell Research Cell lines S114, GTL-16, NCI-H441, and BxPC-3
Concentrations Dissolved in DMSO, final concentrations ~10 μM
Incubation Time 18, or 72 hours
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.
Experimental Result Images Methods Biomarkers Images PMID
Western blot IDO p-Met / Met / p-Akt / Akt / p-ERK / ERK 27082119
Growth inhibition assay Cell proliferation 20603611
In Vivo
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]
Animal Research Animal Models Female athymic mice (nu/nu) bearing S114 or GTL-16 tumor xenografts
Dosages ~30 mg/kg/day
Administration Injection via bolus i.v.

Chemical Information & Solubility

Molecular Weight 641.61 Formula

C32H34Cl2N4O4S
CAS No. 477575-56-7 SDF Download PHA-665752 SDF
Smiles CC1=C(NC(=C1C(=O)N2CCCC2CN3CCCC3)C)C=C4C5=C(C=CC(=C5)S(=O)(=O)CC6=C(C=CC=C6Cl)Cl)NC4=O
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 128 mg/mL ( (199.49 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 10 mg/mL

Water : Insoluble


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In vivo
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Frequently Asked Questions

Question 1:
I need to use S1070 for intraperitoneal application in mice. Could you tell me the solvent you use, please?

Answer:
The highest concentration of PHA-665752 (S1070) in 4% DMSO+30% PEG 300+5% Tween 80+ddH2O is 5mg/ml. If you want to get higher concentration, the concentration of DMSO and PEG will be higher. For example, it can be dissolved in 8% DMSO+50% PEG 300+5% Tween 80+ddH2O at 10mg/ml clearly.

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