PHA-665752

Catalog No.S1070

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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6 Customer Reviews

  • A, SCID mice bearing established HCC827/GR tumor cell xenografts were treated with each drug. The length and width of the tumors were measured at the days indicated and tumor volumes were calculated. The bars represent mean tumor volume ?SD. B, immunohistochemical staining for Ki-67 and TUNEL, as described in Materials and Methods. Quantitative data for proliferation and apoptotic indices are shown as Ki-67+ cells (left) and TUNEL+ cells (right). *, P < 0.01 and **, P < 0.001 for the combination of gefitinib plus NPS-1034 or gefitinib plus PHA-665752 versus either the control or drug alone.

    Cancer Res 2014 74, 253-62. PHA-665752 purchased from Selleck.

    C, Western-blot analysis of MET phosphorylation and its downstream effectors AKT and ERK1/2 in two MET-dependant cell lines (MHCC97H and HCC-3) treated 4 hours with increasing doses of PHA-665752, JNJ-38877605 or tivantinib.

    Clin Cancer Res, 2017. PHA-665752 purchased from Selleck.

  • A, representative Western blot analyses of samples obtained from NSCLC cells exposed to 1 umol/L erlotinib or PHA-665,752 for 6 hours. Levels of total and phosphorylated forms of EGFR, MET, and HER3. B, representative Western blot analyses of samples obtained as described in A showing the levels of EGFR downstream signaling mediators. Protein samples obtained from untreated and treated cells were separated by SDS-PAGE and immunoblotted with each antibody. Tubulin served to ensure equal loading.

    Clin Cancer Res 2014 20, 4806-15. PHA-665752 purchased from Selleck.

    PHA-665752 increases the radiosensitivity and reverses the radioresistance induced by HGF in NPC cells. Radiosensitization induced by PHA-665752 is accompanied by the persistence of the c-H2AX foci. Representative immunofluorescence micrographs of the c-H2AX foci formation in PHA-665752 (1 uM), HGF (20 ng/ml), IR and their combination groups. The micrographs were taken at x 400 magnification.

    Biochem Biophys Res Commun 2014 449(1), 49-54. PHA-665752 purchased from Selleck.

  • Radiosensitization induced by PHA-665752 is accompanied by the persistence of the γ-H2AX foci. (Top) Representative immunofluorescence micrographs of the γ-H2AX foci formation in PHA-665752 (1 uM), HGF (20 ng/ml), IR and their combination groups. The micrographs were taken at x400 magnification. (Bottom) The median number of the γ-H2AX foci per cell. The bars indicate the SD. ∗P < 0.01 compared with the IR alone group.

    Biochem Biophys Res Commun 2014 449, 49-54. PHA-665752 purchased from Selleck.

    Western blot analysis of p-c-Met and c-Met. 0-100μM PHA665752 was added.

     

     

    Dr. Zhang of Tianjin Medical University. PHA-665752 purchased from Selleck.

Purity & Quality Control

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 NFvETJlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MX\JR|UxRTBwMUKzO|Uh|ryP NGrXPYZUSU6JRWK=
LB2241-RCC M3;lU2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{\ybWlEPTB;MD6xOVcxOiEQvF2= NGDwNpBUSU6JRWK=
KINGS-1 MnXzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkLuTWM2OD1yLkO1PVEyKM7:TR?= NEm1Z41USU6JRWK=
ALL-PO Mk\JS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVv2THBJUUN3ME2wMlgyOjd5IN88US=> MlPlV2FPT0WU
SK-LMS-1 MnLzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWfJR|UxRTBwOEm4OFYh|ryP NYW3UWRQW0GQR1XS
MV-4-11 NVnJTWhRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1vicWlEPTB;MT6yPVQ4KM7:TR?= MV7TRW5ITVJ?
SUP-T1 Mn;yS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MonGTWM2OD1{LkGzPVY1KM7:TR?= MonPV2FPT0WU
MRK-nu-1 MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3LWeGlEPTB;Mj60NFA2PiEQvF2= MnXQV2FPT0WU
ES1 NFSyS5BIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGHQ[3dKSzVyPUOuN|Q5PjZizszN NEPzWVNUSU6JRWK=
NOS-1 M2jSRWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NH7BZWJKSzVyPUSuN|k5PjdizszN NUHEc|NDW0GQR1XS
KM12 MnLDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHezUmhKSzVyPUSuOFE5KM7:TR?= NYjWUG9IW0GQR1XS
Becker NIHwZoVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYTteVliUUN3ME21MlI1PjZizszN Ml7nV2FPT0WU
NCI-SNU-1 MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnLmTWM2OD13Lk[zO|M{KM7:TR?= M4XJW3NCVkeHUh?=
EW-22 NUPnbVlZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIXzO|hKSzVyPUeuO|M3OTRizszN MVTTRW5ITVJ?
ES6 MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mlz2TWM2OD15LkixPVUh|ryP M4rrfXNCVkeHUh?=
A498 NFzVVFhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoHUTWM2OD16LkK4OFQ3KM7:TR?= NFHQRYpUSU6JRWK=
EW-16 NWPERoJST3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{P4[mlEPTB;OT62OVQ{KM7:TR?= Mnj4V2FPT0WU
CTV-1 NGHt[pNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NE\h[IhKSzVyPUmuPFUxOjRizszN NUTYenpuW0GQR1XS
ETK-1 NF;Kc2NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmPRTWM2OD1zMD6yPVMyKM7:TR?= NX[xTnp6W0GQR1XS
NCI-H1395 M3TQW2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYW5bWNZUUN3ME2xNE45ODJ2IN88US=> NYnESHBiW0GQR1XS
DOHH-2 MlTLS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWDJR|UxRTFyLkmyOlQh|ryP NWTyUFNIW0GQR1XS
GI-1 NITZVZZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MV7JR|UxRTFzLki1PVYh|ryP M1L1fXNCVkeHUh?=
HT-144 Ml\XS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1qxVWlEPTB;MUSuNlE3OyEQvF2= MmrCV2FPT0WU
ES5 NGjlcWJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MX;JR|UxRTF2LkS2O{DPxE1? Ml7qV2FPT0WU
NALM-6 MnjPS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmrZTWM2OD1zNT6yNVk3KM7:TR?= Mon2V2FPT0WU
KNS-81-FD NVvxd4Z5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGXuXVZKSzVyPUG1MlU5PDlizszN MVHTRW5ITVJ?
TE-15 NFLZdpNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4jneGlEPTB;MU[uOVc4OSEQvF2= NHznZVdUSU6JRWK=
SCC-15 M2nj[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mo\0TWM2OD1zOD6zOFk5KM7:TR?= M1H6UHNCVkeHUh?=
EoL-1-cell NWLIdnJiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFHFOZhKSzVyPUG4MlQ2PDVizszN M{fLZ3NCVkeHUh?=
NCI-H720 NXXDRnI1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnL4TWM2OD1zOD63O|Eh|ryP NHPnU5FUSU6JRWK=
NB14 NVjwOndCT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIPtTZdKSzVyPUG5MlU1OjVizszN M4fGTXNCVkeHUh?=
KE-37 Mn;MS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkPNTWM2OD1zOT64NlM{KM7:TR?= MYfTRW5ITVJ?
LXF-289 NUfi[ZB2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3KyN2lEPTB;MUmuPFYzQSEQvF2= MWHTRW5ITVJ?
RPMI-8402 NWD3XGxFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHn6PG9KSzVyPUKwMlMzPjlizszN MkLjV2FPT0WU
SK-N-DZ M3PNUGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3nzW2lEPTB;MkGuNlE{OSEQvF2= MonFV2FPT0WU
ACN NXfVXIt5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWGwcHlZUUN3ME2yNk4zPDl5IN88US=> M3Plb3NCVkeHUh?=
TE-11 NGi4d4VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3HxXWlEPTB;Mk[uNFY6KM7:TR?= Ml;WV2FPT0WU
COLO-800 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3XS[WlEPTB;MkeuNVch|ryP NUKxV3ZWW0GQR1XS
MOLT-13 Mlm0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmPwTWM2OD1{Nz6xPFQ4KM7:TR?= NIm2SIlUSU6JRWK=
697 NHnFenFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXe0TolDUUN3ME2yPE44PjN|IN88US=> NIKzWldUSU6JRWK=
VA-ES-BJ M{\DfGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWjkWlFnUUN3ME2yPU4{PzJ7IN88US=> M3G0SnNCVkeHUh?=
EW-13 NG\JVItIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXe2OndFUUN3ME2yPU42ODR3IN88US=> NVHRfo43W0GQR1XS
NB7 Mn;TS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYj4TXlSUUN3ME2zNk4zPjZ3IN88US=> MWTTRW5ITVJ?
MONO-MAC-6 M130c2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXjn[5RUUUN3ME2zNk45Pzl3IN88US=> NIfNd2lUSU6JRWK=
SW962 NFTuVpRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnToTWM2OD1|Mz60OVE{KM7:TR?= MWHTRW5ITVJ?
KS-1 MlvIS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlfBTWM2OD1|Mz65OFgyKM7:TR?= NGfGXpZUSU6JRWK=
KU812 NWrVdW5TT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYPJR|UxRTN2LkW3NFIh|ryP M{DTeXNCVkeHUh?=
IMR-5 MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXTvd4ZVUUN3ME2zO{41OzF6IN88US=> M2K0RXNCVkeHUh?=
BC-1 Mk[4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1TRemlEPTB;M{iuNFM{KM7:TR?= NYXaS5h5W0GQR1XS
NCI-H510A MoHoS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1PmRmlEPTB;M{iuNlA{OiEQvF2= M{fNTXNCVkeHUh?=
EW-18 MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYTJR|UxRTRyLkizNFMh|ryP MYXTRW5ITVJ?
CCRF-CEM NXrMU3FwT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWTWbIZKUUN3ME20Nk4zPzl5IN88US=> MUjTRW5ITVJ?
HH Mo\lS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIrRbYhKSzVyPUSzMlUxPjlizszN M1\JdXNCVkeHUh?=
NCI-H2171 M3P1Umdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnfITWM2OD12Nj6wNlczKM7:TR?= NGPqV29USU6JRWK=
LC-2-ad MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3jQXGlEPTB;NEmuNVQyOyEQvF2= M{TSVHNCVkeHUh?=

... Click to View More Cell Line Experimental Data

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]
+ Expand

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]
+ Expand
  • 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]
+ Expand
  • Animal Models: Female athymic mice (nu/nu) bearing S114 or GTL-16 tumor xenografts
  • Formulation: Formulated in vehicle (L-lactate (pH 4.8) and 10% polyethylene glycol)
  • 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 individually and in order:
2% DMSO+castor oil
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
Synonyms N/A

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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

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

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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