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PHA-665752

Name: PHA-665752
Brand: Selleck Chemicals
SKU: S1070
Rating: 5 (79 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 79 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	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?=

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


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

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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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