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 NX\3coxWT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3TYWmlEPTB;MD6xNlM4PSEQvF2= M3zPTnNCVkeHUh?=
LB2241-RCC M4njSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmCxTWM2OD1yLkG1O|AzKM7:TR?= MlLyV2FPT0WU
KINGS-1 Ml74S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mn\aTWM2OD1yLkO1PVEyKM7:TR?= MVfTRW5ITVJ?
ALL-PO MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXTmPGNSUUN3ME2wMlgyOjd5IN88US=> MVnTRW5ITVJ?
SK-LMS-1 M2Pa[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MljGTWM2OD1yLki5PFQ3KM7:TR?= MYnTRW5ITVJ?
MV-4-11 MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M17vSWlEPTB;MT6yPVQ4KM7:TR?= M{XFRnNCVkeHUh?=
SUP-T1 M{LWdWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnXWTWM2OD1{LkGzPVY1KM7:TR?= MlLWV2FPT0WU
MRK-nu-1 MkjrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2TuRmlEPTB;Mj60NFA2PiEQvF2= M{LTWXNCVkeHUh?=
ES1 NWLzPINCT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIG3eZJKSzVyPUOuN|Q5PjZizszN NYm1cJFNW0GQR1XS
NOS-1 MlXpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml;qTWM2OD12LkO5PFY4KM7:TR?= M1L6ZnNCVkeHUh?=
KM12 MoDES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NW\tWFM6UUN3ME20MlQyQCEQvF2= Mn\XV2FPT0WU
Becker NF:zeYZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmjUTWM2OD13LkK0OlYh|ryP NYmyeG5yW0GQR1XS
NCI-SNU-1 M2LFNGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWHJR|UxRTVwNkO3N|Mh|ryP M1HJOHNCVkeHUh?=
EW-22 NI\DZ2RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1L5PGlEPTB;Nz63N|YyPCEQvF2= MWPTRW5ITVJ?
ES6 NYflW4tGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MW\JR|UxRTdwOEG5OUDPxE1? MYfTRW5ITVJ?
A498 M3zCd2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVrLSYl6UUN3ME24MlI5PDR4IN88US=> NYLtPVhnW0GQR1XS
EW-16 MYDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXTJR|UxRTlwNkW0N{DPxE1? MVjTRW5ITVJ?
CTV-1 M{fDUGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWPJR|UxRTlwOEWwNlQh|ryP MVXTRW5ITVJ?
ETK-1 M2rZemdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mlf2TWM2OD1zMD6yPVMyKM7:TR?= NF22dpJUSU6JRWK=
NCI-H1395 NXvvWHZ7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHjCb2lKSzVyPUGwMlgxOjRizszN NF;4bVNUSU6JRWK=
DOHH-2 MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVL1WZhWUUN3ME2xNE46OjZ2IN88US=> MkC3V2FPT0WU
GI-1 NW\ZOGR6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2fadGlEPTB;MUGuPFU6PiEQvF2= MmDJV2FPT0WU
HT-144 MnuxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFHXUlFKSzVyPUG0MlIyPjNizszN MmPzV2FPT0WU
ES5 MnXoS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXrJR|UxRTF2LkS2O{DPxE1? NFH5OXVUSU6JRWK=
NALM-6 Mmi3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFvSeVhKSzVyPUG1MlIyQTZizszN Mk[2V2FPT0WU
KNS-81-FD MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MorrTWM2OD1zNT61PFQ6KM7:TR?= NHn4c2VUSU6JRWK=
TE-15 NVjvfVVHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWD2WHdYUUN3ME2xOk42PzdzIN88US=> M{nNS3NCVkeHUh?=
SCC-15 MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYOwUoxyUUN3ME2xPE4{PDl6IN88US=> MYnTRW5ITVJ?
EoL-1-cell M1;me2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHzlepBKSzVyPUG4MlQ2PDVizszN MVvTRW5ITVJ?
NCI-H720 MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3PUeWlEPTB;MUiuO|cyKM7:TR?= MVvTRW5ITVJ?
NB14 MlGzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYXJR|UxRTF7LkW0NlUh|ryP Ml;RV2FPT0WU
KE-37 NF7qNHJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIPKSY9KSzVyPUG5MlgzOzNizszN NH\JU2ZUSU6JRWK=
LXF-289 NFvrR2tIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHX0TGZKSzVyPUG5Mlg3OjlizszN M{LIT3NCVkeHUh?=
RPMI-8402 NXnXZWl3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVzJR|UxRTJyLkOyOlkh|ryP MlzYV2FPT0WU
SK-N-DZ M133fWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3vW[mlEPTB;MkGuNlE{OSEQvF2= MmO3V2FPT0WU
ACN MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX;hUplEUUN3ME2yNk4zPDl5IN88US=> NFG5WlRUSU6JRWK=
TE-11 MnTpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2T4W2lEPTB;Mk[uNFY6KM7:TR?= NVO4O2JvW0GQR1XS
COLO-800 MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmHOTWM2OD1{Nz6xO{DPxE1? MmjHV2FPT0WU
MOLT-13 NVm4WIt6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH3JcXFKSzVyPUK3MlE5PDdizszN NEWzO2dUSU6JRWK=
697 MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYPJR|UxRTJ6Lke2N|Mh|ryP M{POcnNCVkeHUh?=
VA-ES-BJ MYDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4XrV2lEPTB;MkmuN|czQSEQvF2= MkXQV2FPT0WU
EW-13 MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4XiSWlEPTB;MkmuOVA1PSEQvF2= M4K3TnNCVkeHUh?=
NB7 MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYnCdVJHUUN3ME2zNk4zPjZ3IN88US=> M3zNSnNCVkeHUh?=
MONO-MAC-6 NYjlVpdYT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoqxTWM2OD1|Mj64O|k2KM7:TR?= MonwV2FPT0WU
SW962 MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUPJR|UxRTN|LkS1NVMh|ryP NUfZT21kW0GQR1XS
KS-1 M3HXUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHOyOHhKSzVyPUOzMlk1QDFizszN MV;TRW5ITVJ?
KU812 MV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUjJR|UxRTN2LkW3NFIh|ryP MVHTRW5ITVJ?
IMR-5 MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1rCO2lEPTB;M{euOFMyQCEQvF2= M{O1U3NCVkeHUh?=
BC-1 NHHPfVNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NX\mTXBxUUN3ME2zPE4xOzNizszN NIT1[FBUSU6JRWK=
NCI-H510A M4jaOmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUHJR|UxRTN6LkKwN|Ih|ryP MV\TRW5ITVJ?
EW-18 MX7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWHyd2NXUUN3ME20NE45OzB|IN88US=> Mn[2V2FPT0WU
CCRF-CEM M2\He2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MonZTWM2OD12Mj6yO|k4KM7:TR?= NVmyXIpuW0GQR1XS
HH M{X2d2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVXUNVE6UUN3ME20N{42ODZ7IN88US=> NGHiU3hUSU6JRWK=
NCI-H2171 M1X5dmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFXIUZNKSzVyPUS2MlAzPzJizszN NI\wWG1USU6JRWK=
LC-2-ad MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M13z[WlEPTB;NEmuNVQyOyEQvF2= NFXmfopUSU6JRWK=

... 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