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 78 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 NU\WZ4xpT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoPlTWM2OD1yLkGyN|c2KM7:TR?= NVjzdo41W0GQR1XS
LB2241-RCC NH3jOGNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mnf0TWM2OD1yLkG1O|AzKM7:TR?= MUDTRW5ITVJ?
KINGS-1 MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{jUdWlEPTB;MD6zOVkyOSEQvF2= MVfTRW5ITVJ?
ALL-PO NY\jO4VVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3rvZmlEPTB;MD64NVI4PyEQvF2= NYfJSmZWW0GQR1XS
SK-LMS-1 NFfXdJJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVjjbGQ5UUN3ME2wMlg6QDR4IN88US=> MnzvV2FPT0WU
MV-4-11 MljHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MonWTWM2OD1zLkK5OFch|ryP M1LW[nNCVkeHUh?=
SUP-T1 NEn1Wo9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFXoSGdKSzVyPUKuNVM6PjRizszN NV:3NpkxW0GQR1XS
MRK-nu-1 NXWxcWt[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkTrTWM2OD1{LkSwNFU3KM7:TR?= NVW0d5VtW0GQR1XS
ES1 NGi1d2VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4rD[2lEPTB;Mz6zOFg3PiEQvF2= M4rWVnNCVkeHUh?=
NOS-1 MojmS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXm2Z4NLUUN3ME20MlM6QDZ5IN88US=> M2fT[nNCVkeHUh?=
KM12 NUnaXnQyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGXwSJRKSzVyPUSuOFE5KM7:TR?= MnXNV2FPT0WU
Becker NIDaT3ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUTrN5BsUUN3ME21MlI1PjZizszN NX3ifI1sW0GQR1XS
NCI-SNU-1 NIrSUIlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NV:wfpUxUUN3ME21MlY{PzN|IN88US=> M1SzdHNCVkeHUh?=
EW-22 Ml[2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXHYRWJmUUN3ME23Mlc{PjF2IN88US=> NULZZo85W0GQR1XS
ES6 MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NULtZZcyUUN3ME23MlgyQTVizszN M3vtNXNCVkeHUh?=
A498 M{H1OGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MorzTWM2OD16LkK4OFQ3KM7:TR?= MkewV2FPT0WU
EW-16 MnrhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEfoNoJKSzVyPUmuOlU1OyEQvF2= M4npVHNCVkeHUh?=
CTV-1 MomxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mle1TWM2OD17Lki1NFI1KM7:TR?= NUHBOWNmW0GQR1XS
ETK-1 NV;RV3k{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2i2eGlEPTB;MUCuNlk{OSEQvF2= M4HMO3NCVkeHUh?=
NCI-H1395 NUK1XZozT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHLLc21KSzVyPUGwMlgxOjRizszN M1THO3NCVkeHUh?=
DOHH-2 NU[yXGFiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoPsTWM2OD1zMD65NlY1KM7:TR?= M3S0OHNCVkeHUh?=
GI-1 MYDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NF\Qfo1KSzVyPUGxMlg2QTZizszN M3nzOXNCVkeHUh?=
HT-144 NHLzbYVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFnSdXZKSzVyPUG0MlIyPjNizszN M3jNUnNCVkeHUh?=
ES5 MmLFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlLiTWM2OD1zND60Olch|ryP NVHmV29FW0GQR1XS
NALM-6 NV7oVXlpT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1vQcmlEPTB;MUWuNlE6PiEQvF2= MmL0V2FPT0WU
KNS-81-FD NEW5eY5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NF3PcHBKSzVyPUG1MlU5PDlizszN NHjCSZpUSU6JRWK=
TE-15 NHLVZndIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUHUT|dSUUN3ME2xOk42PzdzIN88US=> M2fTUnNCVkeHUh?=
SCC-15 NIjOOWJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVLlbZR[UUN3ME2xPE4{PDl6IN88US=> MWPTRW5ITVJ?
EoL-1-cell M4nme2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mmj3TWM2OD1zOD60OVQ2KM7:TR?= MYjTRW5ITVJ?
NCI-H720 NHqyXJdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mk\5TWM2OD1zOD63O|Eh|ryP M3PmR3NCVkeHUh?=
NB14 M4G0NGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXHJR|UxRTF7LkW0NlUh|ryP NHXZPZNUSU6JRWK=
KE-37 MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mmr4TWM2OD1zOT64NlM{KM7:TR?= MmjkV2FPT0WU
LXF-289 MmHWS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnexTWM2OD1zOT64OlI6KM7:TR?= NGPwe3dUSU6JRWK=
RPMI-8402 Mn;RS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mkn5TWM2OD1{MD6zNlY6KM7:TR?= MVTTRW5ITVJ?
SK-N-DZ NYnqSZBKT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXLVW25PUUN3ME2yNU4zOTNzIN88US=> MYnTRW5ITVJ?
ACN MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1fEb2lEPTB;MkKuNlQ6PyEQvF2= MVfTRW5ITVJ?
TE-11 Mk\XS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFjaUmdKSzVyPUK2MlA3QSEQvF2= MXXTRW5ITVJ?
COLO-800 NYHFRox7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVr3eok6UUN3ME2yO{4yPyEQvF2= NX70TIJmW0GQR1XS
MOLT-13 NFSwcWdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmK3TWM2OD1{Nz6xPFQ4KM7:TR?= MmPRV2FPT0WU
697 MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYPWSo5uUUN3ME2yPE44PjN|IN88US=> Mk\3V2FPT0WU
VA-ES-BJ M{D1e2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1fLSmlEPTB;MkmuN|czQSEQvF2= MWfTRW5ITVJ?
EW-13 NX\aTlZJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MV\JR|UxRTJ7LkWwOFUh|ryP M3zZTnNCVkeHUh?=
NB7 MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NF:3dmZKSzVyPUOyMlI3PjVizszN NEjnbFVUSU6JRWK=
MONO-MAC-6 MWDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWO2NGppUUN3ME2zNk45Pzl3IN88US=> NEOxWldUSU6JRWK=
SW962 NGK2[G9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVvwclh{UUN3ME2zN{41PTF|IN88US=> MkGxV2FPT0WU
KS-1 M2W0emdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NF;sOmRKSzVyPUOzMlk1QDFizszN MYLTRW5ITVJ?
KU812 Ml\QS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmX0TWM2OD1|ND61O|AzKM7:TR?= Mom1V2FPT0WU
IMR-5 NVjsdJBjT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3L0[GlEPTB;M{euOFMyQCEQvF2= MX7TRW5ITVJ?
BC-1 M2XtNWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFnt[mFKSzVyPUO4MlA{OyEQvF2= NE\WZYRUSU6JRWK=
NCI-H510A MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NF3md4JKSzVyPUO4MlIxOzJizszN M16yfXNCVkeHUh?=
EW-18 Mmn6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVjBUppwUUN3ME20NE45OzB|IN88US=> MoLNV2FPT0WU
CCRF-CEM MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWrJR|UxRTR{LkK3PVch|ryP MUXTRW5ITVJ?
HH M4Tqbmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Ml34TWM2OD12Mz61NFY6KM7:TR?= MULTRW5ITVJ?
NCI-H2171 NGraeXhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{XpdWlEPTB;NE[uNFI4OiEQvF2= MmP0V2FPT0WU
LC-2-ad MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnjvTWM2OD12OT6xOFE{KM7:TR?= NHuwbmRUSU6JRWK=
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

DMSO 128 mg/mL
(199.49 mM)
Water Insoluble
Ethanol Insoluble

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)

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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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