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, 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.

    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, 23(15):4364-4375. 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 MmnwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHTuS2hKSzVyPUCuNVI{PzVizszN NVL2XI1nW0GQR1XS
LB2241-RCC NETVb5ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlXZTWM2OD1yLkG1O|AzKM7:TR?= NGDGXm9USU6JRWK=
KINGS-1 NU\ETJFyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIC1b|RKSzVyPUCuN|U6OTFizszN MXvTRW5ITVJ?
ALL-PO M{jlN2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGTIR3JKSzVyPUCuPFEzPzdizszN NFvxV5NUSU6JRWK=
SK-LMS-1 NWfzZoF3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnHoTWM2OD1yLki5PFQ3KM7:TR?= NXfSWWJUW0GQR1XS
MV-4-11 MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUTvd3pUUUN3ME2xMlI6PDdizszN NGDVR49USU6JRWK=
SUP-T1 M3XMNmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{DYbmlEPTB;Mj6xN|k3PCEQvF2= Mn\1V2FPT0WU
MRK-nu-1 NGjRfoRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFPrclVKSzVyPUKuOFAxPTZizszN NHP4SmpUSU6JRWK=
ES1 NV;yW281T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVvJR|UxRTNwM{S4OlYh|ryP NELDZm5USU6JRWK=
NOS-1 Mnf6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MonnTWM2OD12LkO5PFY4KM7:TR?= MnTXV2FPT0WU
KM12 NF:2VHJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnPRTWM2OD12LkSxPEDPxE1? NHrPcZJUSU6JRWK=
Becker NH7QZ41Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnToTWM2OD13LkK0OlYh|ryP NIrJbmtUSU6JRWK=
NCI-SNU-1 NWHTcnhST3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MV\JR|UxRTVwNkO3N|Mh|ryP NVfLSJloW0GQR1XS
EW-22 MkXXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUDJR|UxRTdwN{O2NVQh|ryP MV\TRW5ITVJ?
ES6 NXn0VlI{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MV;JR|UxRTdwOEG5OUDPxE1? NImyUGxUSU6JRWK=
A498 M2LQSmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4HhWGlEPTB;OD6yPFQ1PiEQvF2= MmX2V2FPT0WU
EW-16 NVvRbGVET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUHJR|UxRTlwNkW0N{DPxE1? MnTLV2FPT0WU
CTV-1 Mn7mS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWrNfoxEUUN3ME25Mlg2ODJ2IN88US=> MVHTRW5ITVJ?
ETK-1 NGjrdWFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIXjTI5KSzVyPUGwMlI6OzFizszN Mlr2V2FPT0WU
NCI-H1395 NXrFWVAyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1vuZ2lEPTB;MUCuPFAzPCEQvF2= NV34eJc6W0GQR1XS
DOHH-2 NH\mXWhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NETw[lFKSzVyPUGwMlkzPjRizszN MnXoV2FPT0WU
GI-1 NWLBbXZET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MV;JR|UxRTFzLki1PVYh|ryP MXfTRW5ITVJ?
HT-144 M{fJTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVnJR|UxRTF2LkKxOlMh|ryP NEfmbYtUSU6JRWK=
ES5 M2DxTWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUTJR|UxRTF2LkS2O{DPxE1? NYj4bJhsW0GQR1XS
NALM-6 NGLZcJBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXvnXIRXUUN3ME2xOU4zOTl4IN88US=> NHvsSJJUSU6JRWK=
KNS-81-FD MkDJS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYLJR|UxRTF3LkW4OFkh|ryP NYSzT5NiW0GQR1XS
TE-15 MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYD2XGxpUUN3ME2xOk42PzdzIN88US=> NELtR2ZUSU6JRWK=
SCC-15 Mmq2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmjyTWM2OD1zOD6zOFk5KM7:TR?= MWnTRW5ITVJ?
EoL-1-cell M{K2R2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1P0ZmlEPTB;MUiuOFU1PSEQvF2= MVnTRW5ITVJ?
NCI-H720 M2rpTWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmLGTWM2OD1zOD63O|Eh|ryP NYPxUoZZW0GQR1XS
NB14 MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3fLO2lEPTB;MUmuOVQzPSEQvF2= M4XHe3NCVkeHUh?=
KE-37 MnK2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3eyPGlEPTB;MUmuPFI{OyEQvF2= MlXJV2FPT0WU
LXF-289 MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkDpTWM2OD1zOT64OlI6KM7:TR?= M1fpbHNCVkeHUh?=
RPMI-8402 NYO0PI9kT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkT1TWM2OD1{MD6zNlY6KM7:TR?= M164NnNCVkeHUh?=
SK-N-DZ NFTZUWFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1;IWmlEPTB;MkGuNlE{OSEQvF2= MmixV2FPT0WU
ACN NGfnV3ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnrJTWM2OD1{Mj6yOFk4KM7:TR?= NGLJOVlUSU6JRWK=
TE-11 MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnvhTWM2OD1{Nj6wOlkh|ryP NGq3Z|JUSU6JRWK=
COLO-800 MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGq3[FZKSzVyPUK3MlE4KM7:TR?= M{HodnNCVkeHUh?=
MOLT-13 M4q4S2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGPTclRKSzVyPUK3MlE5PDdizszN MVfTRW5ITVJ?
697 MkG4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmTETWM2OD1{OD63OlM{KM7:TR?= MlnZV2FPT0WU
VA-ES-BJ NUfnRmJ6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVvEeHNlUUN3ME2yPU4{PzJ7IN88US=> NW\QcGE4W0GQR1XS
EW-13 NHu0XY9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHnSSFNKSzVyPUK5MlUxPDVizszN NFOxUFhUSU6JRWK=
NB7 MlPFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYLJR|UxRTN{LkK2OlUh|ryP MWjTRW5ITVJ?
MONO-MAC-6 M2nSemdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWf2eIt6UUN3ME2zNk45Pzl3IN88US=> NXrZRlh4W0GQR1XS
SW962 M{fvPWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmDTTWM2OD1|Mz60OVE{KM7:TR?= NYPzTY5XW0GQR1XS
KS-1 MkDyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXjJR|UxRTN|Lkm0PFEh|ryP NETme4RUSU6JRWK=
KU812 M{H5XWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2nwXWlEPTB;M{SuOVcxOiEQvF2= M{LwT3NCVkeHUh?=
IMR-5 M1TRTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYTJR|UxRTN5LkSzNVgh|ryP NVzrUotXW0GQR1XS
BC-1 MmPnS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFLDN|lKSzVyPUO4MlA{OyEQvF2= MVHTRW5ITVJ?
NCI-H510A NF22PJJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFXtdVhKSzVyPUO4MlIxOzJizszN MXTTRW5ITVJ?
EW-18 M2O3Omdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHrsd2xKSzVyPUSwMlg{ODNizszN MmPPV2FPT0WU
CCRF-CEM M3v0dWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnjnTWM2OD12Mj6yO|k4KM7:TR?= NYK4eVlGW0GQR1XS
HH NY\hSXlHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlO5TWM2OD12Mz61NFY6KM7:TR?= Mn6zV2FPT0WU
NCI-H2171 M2e5fGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHXnOY5KSzVyPUS2MlAzPzJizszN M{S5[HNCVkeHUh?=
LC-2-ad MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYeyNHdSUUN3ME20PU4yPDF|IN88US=> NWLw[I9kW0GQR1XS

... 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 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

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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