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PHA-665752

Name: PHA-665752
Brand: Selleck Chemicals
SKU: S1070
Rating: 5 (78 reviews)

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.

CAS No. 477575-56-7

Selleck's PHA-665752 has been cited by 78 publications

Purity & Quality Control

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c-Met Signaling Pathway Map

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 K_i 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=

Click to View More Cell Line Experimental Data

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.

References

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. Click to purchase: Castor Oil	5mg/mL

Chemical Information

Molecular Weight	641.61
Formula	C₃₂H₃₄Cl₂N₄O₄S
CAS No.	477575-56-7
Storage	3 years	-20°C	powder
Storage	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

Download PHA-665752 SDF

In vivo Formulation Calculator (Clear solution)

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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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