PHA-665752

For research use only.

Catalog No.S1070

50 publications

PHA-665752 Chemical Structure

Molecular Weight(MW): 641.61

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.

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Selleck's PHA-665752 has been cited by 50 publications

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Choose Selective c-Met Inhibitors

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 NFG2OIVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXLj[WtDUUN3ME2wMlEzOzd3IN88US=> MYrTRW5ITVJ?
LB2241-RCC MoX2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkDnTWM2OD1yLkG1O|AzKM7:TR?= MoTPV2FPT0WU
KINGS-1 MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3G0TGlEPTB;MD6zOVkyOSEQvF2= MkLqV2FPT0WU
ALL-PO M{G1cmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoriTWM2OD1yLkixNlc4KM7:TR?= NEiwSmNUSU6JRWK=
SK-LMS-1 M1v6b2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4\VO2lEPTB;MD64PVg1PiEQvF2= M1HoS3NCVkeHUh?=
MV-4-11 M{fqZmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4nUe2lEPTB;MT6yPVQ4KM7:TR?= M17zZ3NCVkeHUh?=
SUP-T1 MoTLS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NV3Dc2ZRUUN3ME2yMlE{QTZ2IN88US=> NUfVR3lTW0GQR1XS
MRK-nu-1 NYm0XYMzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFXadIpKSzVyPUKuOFAxPTZizszN Mln6V2FPT0WU
ES1 NFf4WWpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3rVS2lEPTB;Mz6zOFg3PiEQvF2= M1HBdHNCVkeHUh?=
NOS-1 MnXUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmTjTWM2OD12LkO5PFY4KM7:TR?= MUjTRW5ITVJ?
KM12 M2LHeGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4PFWWlEPTB;ND60NVgh|ryP MlXYV2FPT0WU
Becker MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEnDXVBKSzVyPUWuNlQ3PiEQvF2= NWGycWtrW0GQR1XS
NCI-SNU-1 M3fDcmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4jTcWlEPTB;NT62N|c{OyEQvF2= M2DsWHNCVkeHUh?=
EW-22 NHrncYJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmrBTWM2OD15LkezOlE1KM7:TR?= NELObG5USU6JRWK=
ES6 NXGyWpVtT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHrSRWNKSzVyPUeuPFE6PSEQvF2= NEfkTZdUSU6JRWK=
A498 MnXJS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1\Qc2lEPTB;OD6yPFQ1PiEQvF2= M3G4dnNCVkeHUh?=
EW-16 Mn34S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MW\JR|UxRTlwNkW0N{DPxE1? NHLzVnBUSU6JRWK=
CTV-1 NIfKcppIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2K4SmlEPTB;OT64OVAzPCEQvF2= M1i3enNCVkeHUh?=
ETK-1 MlriS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MV7JR|UxRTFyLkK5N|Eh|ryP MmrlV2FPT0WU
NCI-H1395 NGLIdWRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlzGTWM2OD1zMD64NFI1KM7:TR?= M3XVenNCVkeHUh?=
DOHH-2 NV;qPYpkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MX\JR|UxRTFyLkmyOlQh|ryP NEjWUolUSU6JRWK=
GI-1 MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Ml25TWM2OD1zMT64OVk3KM7:TR?= M3vEZnNCVkeHUh?=
HT-144 MnrFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NX:xRXRVUUN3ME2xOE4zOTZ|IN88US=> Mn7sV2FPT0WU
ES5 M3LpTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MY\JR|UxRTF2LkS2O{DPxE1? NVHxcoE{W0GQR1XS
NALM-6 M1fremdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4TDO2lEPTB;MUWuNlE6PiEQvF2= NWru[WNrW0GQR1XS
KNS-81-FD M4TMTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnrtTWM2OD1zNT61PFQ6KM7:TR?= NEjMS21USU6JRWK=
TE-15 NYC4ZnBUT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3vPXWlEPTB;MU[uOVc4OSEQvF2= NUm1d5hMW0GQR1XS
SCC-15 NWW1PZprT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXXJR|UxRTF6LkO0PVgh|ryP NUDid2VpW0GQR1XS
EoL-1-cell NUXYd49oT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mlv3TWM2OD1zOD60OVQ2KM7:TR?= MWjTRW5ITVJ?
NCI-H720 Ml3pS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWPJR|UxRTF6Lke3NUDPxE1? MnHUV2FPT0WU
NB14 NUnW[3BGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4nUPWlEPTB;MUmuOVQzPSEQvF2= NInhT5NUSU6JRWK=
KE-37 NHfB[lRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2nKO2lEPTB;MUmuPFI{OyEQvF2= M2[2d3NCVkeHUh?=
LXF-289 Mm[xS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NELVdVFKSzVyPUG5Mlg3OjlizszN NYD5dFEzW0GQR1XS
RPMI-8402 MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWHD[ZRQUUN3ME2yNE4{OjZ7IN88US=> MV7TRW5ITVJ?
SK-N-DZ NFzESlZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWXJR|UxRTJzLkKxN|Eh|ryP M2XoSHNCVkeHUh?=
ACN MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVrJR|UxRTJ{LkK0PVch|ryP NXf3S|F[W0GQR1XS
TE-11 M37u[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MX;JR|UxRTJ4LkC2PUDPxE1? Ml;lV2FPT0WU
COLO-800 M2DobWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXzJR|UxRTJ5LkG3JO69VQ>? M3jjNXNCVkeHUh?=
MOLT-13 Mme0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXzjOol6UUN3ME2yO{4yQDR5IN88US=> M3WzNXNCVkeHUh?=
697 NX3jPWJ5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHniWlZKSzVyPUK4Mlc3OzNizszN MlP0V2FPT0WU
VA-ES-BJ NEC0NYRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXjJR|UxRTJ7LkO3Nlkh|ryP NIi0NZlUSU6JRWK=
EW-13 MlPJS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUHqXoVGUUN3ME2yPU42ODR3IN88US=> M1:4R3NCVkeHUh?=
NB7 M2S0Zmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIjtUWZKSzVyPUOyMlI3PjVizszN NWOwVpNrW0GQR1XS
MONO-MAC-6 NFz0SY1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXfFRXBvUUN3ME2zNk45Pzl3IN88US=> MoKzV2FPT0WU
SW962 NG\PU2RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUXJR|UxRTN|LkS1NVMh|ryP MWXTRW5ITVJ?
KS-1 MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFKw[GVKSzVyPUOzMlk1QDFizszN M2nHZnNCVkeHUh?=
KU812 Mk\SS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYfCfYRZUUN3ME2zOE42PzB{IN88US=> NFHxUGNUSU6JRWK=
IMR-5 NILTTGNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWfncnQxUUN3ME2zO{41OzF6IN88US=> MoWzV2FPT0WU
BC-1 NIL0fWxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYPJR|UxRTN6LkCzN{DPxE1? M1vRWHNCVkeHUh?=
NCI-H510A MkLHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXvF[pU3UUN3ME2zPE4zODN{IN88US=> MlS5V2FPT0WU
EW-18 MmDWS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXfyfXd1UUN3ME20NE45OzB|IN88US=> M1PEXHNCVkeHUh?=
CCRF-CEM MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYPJR|UxRTR{LkK3PVch|ryP MXvTRW5ITVJ?
HH MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnLVTWM2OD12Mz61NFY6KM7:TR?= M1X3VHNCVkeHUh?=
NCI-H2171 NYnvSGVVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlP3TWM2OD12Nj6wNlczKM7:TR?= NIDqT3BUSU6JRWK=
LC-2-ad MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{iyTGlEPTB;NEmuNVQyOyEQvF2= NX72OZVPW0GQR1XS

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
IDO; 

PubMed: 27082119     


PHA-665752 inhibited both c-Met phosphorylation and IDO expression of SKOV-3 cells in a concentration-dependent manner.

p-Met / Met / p-Akt / Akt / p-ERK / ERK ; 

PubMed: 25226813     


HCC827 GR6 cells were treated for 6 h with increasing concentrations of tivantinib or PHA-665752. Cell lysates were immunoblotted to detect indicated proteins. PHA-665752 partially inhibits MET and ERK1/2 phosphorylation but not AKT. Tivantinib did not inhibit MET phosphorylation or downstream signaling.

27082119 25226813
Growth inhibition assay
Cell proliferation ; 

PubMed: 20603611     


Cell proliferation was evaluated at fixed times after the addition of HGF (50 ng/ml) +/− PHA-665752 (d) at different concentrations in 2% FBS-containing medium. PHA-665752 showed a marked reduction in cell numbers starting from 24 h at micromolar concentrations (5 and 10 μ), whereas lower concentrations did not exert a significant reduction of proliferation with respect to the control. 

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

Kinase Assay:[1]
- Collapse

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]
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  • 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.
    (Only for Reference)
Animal Research:[1]
- Collapse
  • 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.
    (Only for Reference)

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

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 641.61
Formula

C32H34Cl2N4O4S

CAS No. 477575-56-7
Storage powder
in solvent
Synonyms N/A
Smiles CC1=C(C(=C([NH]1)/C=C/2C(=O)NC3=C2C=C(C=C3)[S](=O)(=O)CC4=C(Cl)C=CC=C4Cl)C)C(=O)N5CCCC5CN6CCCC6

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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.

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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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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID