PHA-665752

Catalog No.S1070

For research use only.

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

CAS No. 477575-56-7

Selleck's PHA-665752 has been cited by 79 publications

Purity & Quality Control

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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

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]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
NCI-SNU-5 M{DORmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2q2U2lEPTB;MD6xNlM4PSEQvF2= Mn2xV2FPT0WU
LB2241-RCC MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXnXVGg6UUN3ME2wMlE2PzB{IN88US=> M3Pp[XNCVkeHUh?=
KINGS-1 Mk\2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWPJ[Yk6UUN3ME2wMlM2QTFzIN88US=> Ml2yV2FPT0WU
ALL-PO M3f1bWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUmwPYNvUUN3ME2wMlgyOjd5IN88US=> NXHpXGtKW0GQR1XS
SK-LMS-1 M1fJXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXPJR|UxRTBwOEm4OFYh|ryP NYrK[3FUW0GQR1XS
MV-4-11 NFS5UXVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWPoOHN4UUN3ME2xMlI6PDdizszN NF[0fG9USU6JRWK=
SUP-T1 M4fyNGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUjJR|UxRTJwMUO5OlQh|ryP NHvMNGJUSU6JRWK=
MRK-nu-1 NIruXVRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NW\5[IJMUUN3ME2yMlQxODV4IN88US=> MYrTRW5ITVJ?
ES1 M2Xn[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1nxVmlEPTB;Mz6zOFg3PiEQvF2= NYnkcoVXW0GQR1XS
NOS-1 NHLTdG1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHfBWHFKSzVyPUSuN|k5PjdizszN NInLfHVUSU6JRWK=
KM12 M2[2Wmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmPtTWM2OD12LkSxPEDPxE1? Mn;ZV2FPT0WU
Becker M2HlV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYTRfVY1UUN3ME21MlI1PjZizszN MWjTRW5ITVJ?
NCI-SNU-1 MmXjS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUfJR|UxRTVwNkO3N|Mh|ryP MULTRW5ITVJ?
EW-22 M33CWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkLYTWM2OD15LkezOlE1KM7:TR?= NID1dYJUSU6JRWK=
ES6 MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYfJR|UxRTdwOEG5OUDPxE1? NH:yZWhUSU6JRWK=
A498 Mom3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUfvb4hmUUN3ME24MlI5PDR4IN88US=> NVu2VXR1W0GQR1XS
EW-16 MlfNS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWXkV2k2UUN3ME25MlY2PDNizszN MlTLV2FPT0WU
CTV-1 M4rYW2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlztTWM2OD17Lki1NFI1KM7:TR?= NHr1V2RUSU6JRWK=
ETK-1 M4LoWGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1\j[GlEPTB;MUCuNlk{OSEQvF2= NXHlRWVXW0GQR1XS
NCI-H1395 NH\HcldIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkHlTWM2OD1zMD64NFI1KM7:TR?= M3iz[3NCVkeHUh?=
DOHH-2 M1zFXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWC5TmdNUUN3ME2xNE46OjZ2IN88US=> M{HBV3NCVkeHUh?=
GI-1 NYPpZW9xT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{\PcWlEPTB;MUGuPFU6PiEQvF2= NXrrT|RLW0GQR1XS
HT-144 MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NV\5RpZtUUN3ME2xOE4zOTZ|IN88US=> M{XGRnNCVkeHUh?=
ES5 NEHESoJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NF;MRY9KSzVyPUG0MlQ3PyEQvF2= NV64cGV6W0GQR1XS
NALM-6 M4eySGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmfyTWM2OD1zNT6yNVk3KM7:TR?= M1LXVXNCVkeHUh?=
KNS-81-FD MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mnj2TWM2OD1zNT61PFQ6KM7:TR?= NF;weZJUSU6JRWK=
TE-15 Mn63S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmrjTWM2OD1zNj61O|cyKM7:TR?= Mn:0V2FPT0WU
SCC-15 MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoPYTWM2OD1zOD6zOFk5KM7:TR?= NFToOZlUSU6JRWK=
EoL-1-cell MoXjS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIW0SJhKSzVyPUG4MlQ2PDVizszN M{fOO3NCVkeHUh?=
NCI-H720 MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{\Xd2lEPTB;MUiuO|cyKM7:TR?= M{C3dHNCVkeHUh?=
NB14 NHnWWoZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVrJR|UxRTF7LkW0NlUh|ryP M2m1fXNCVkeHUh?=
KE-37 MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NF3T[WtKSzVyPUG5MlgzOzNizszN NVzQUoNbW0GQR1XS
LXF-289 M{nTeWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmTBTWM2OD1zOT64OlI6KM7:TR?= MkD6V2FPT0WU
RPMI-8402 NXeyfpZFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{SydGlEPTB;MkCuN|I3QSEQvF2= Mly2V2FPT0WU
SK-N-DZ MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVnJR|UxRTJzLkKxN|Eh|ryP NH\tTXZUSU6JRWK=
ACN M2TVSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1ns[mlEPTB;MkKuNlQ6PyEQvF2= NGfOT5JUSU6JRWK=
TE-11 MnTSS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmPzTWM2OD1{Nj6wOlkh|ryP M2rGOHNCVkeHUh?=
COLO-800 NEXBNYpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4Lu[mlEPTB;MkeuNVch|ryP NIrsR2tUSU6JRWK=
MOLT-13 MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{PXO2lEPTB;MkeuNVg1PyEQvF2= NG\oOYhUSU6JRWK=
697 MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1HoPWlEPTB;MkiuO|Y{OyEQvF2= NIH2fI9USU6JRWK=
VA-ES-BJ MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2\MTmlEPTB;MkmuN|czQSEQvF2= MlzJV2FPT0WU
EW-13 NUDLTIdOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1;WWWlEPTB;MkmuOVA1PSEQvF2= NECwfmxUSU6JRWK=
NB7 MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXzJR|UxRTN{LkK2OlUh|ryP M{TFVnNCVkeHUh?=
MONO-MAC-6 MYrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX7oTpFrUUN3ME2zNk45Pzl3IN88US=> MUTTRW5ITVJ?
SW962 NIPIS5BIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3TGXmlEPTB;M{OuOFUyOyEQvF2= MlS3V2FPT0WU
KS-1 MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUHmdWxuUUN3ME2zN{46PDhzIN88US=> MVfTRW5ITVJ?
KU812 M2\DbGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M336UWlEPTB;M{SuOVcxOiEQvF2= NXrtOWluW0GQR1XS
IMR-5 MkLVS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{n1[mlEPTB;M{euOFMyQCEQvF2= MnLiV2FPT0WU
BC-1 NEnTNllIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2jGT2lEPTB;M{iuNFM{KM7:TR?= NHjGe4NUSU6JRWK=
NCI-H510A M1XqR2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NV:0WlFEUUN3ME2zPE4zODN{IN88US=> NGWwO4xUSU6JRWK=
EW-18 MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1v6OmlEPTB;NECuPFMxOyEQvF2= MX3TRW5ITVJ?
CCRF-CEM MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MV3JR|UxRTR{LkK3PVch|ryP Mn;JV2FPT0WU
HH NHTBVVFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWXJR|UxRTR|LkWwOlkh|ryP NV;oN2hRW0GQR1XS
NCI-H2171 NFHlNI9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYjJR|UxRTR4LkCyO|Ih|ryP M2HpfHNCVkeHUh?=
LC-2-ad M{Tndmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NF\2UIVKSzVyPUS5MlE1OTNizszN M1zST3NCVkeHUh?=
Assay
Methods Test Index PMID
Western blot p-Met / Met / p-Akt / Akt / p-ERK / ERK ; IDO 25226813 27082119
Growth inhibition assay Cell proliferation 20603611
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]

Protocol (from reference)

Kinase Assay:[1]
  • 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:[1]
  • 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.
Animal Research:[1]
  • 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.

Solubility (25°C)

In vitro

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
2% DMSO+castor oil
For best results, use promptly after mixing.

5mg/mL

Chemical Information

Molecular Weight 641.61
Formula

C32H34Cl2N4O4S

CAS No. 477575-56-7
Storage 3 years -20°C powder
2 years -80°C in solvent
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

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

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% DMSO % % Tween 80 % ddH2O
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Working concentration: mg/ml;

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.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

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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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