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.

Size Price Stock Quantity  
USD 70 In stock
USD 120 In stock
USD 470 In stock
USD 997 In stock
Bulk Discount

Free Overnight Delivery on orders over $ 500
Next day delivery by 10:00 a.m. Order now.

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 NXS0cZJqT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NE\KTXVKSzVyPUCuNVI{PzVizszN NHHpdFhUSU6JRWK=
LB2241-RCC M{TIO2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkjhTWM2OD1yLkG1O|AzKM7:TR?= MULTRW5ITVJ?
KINGS-1 MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NY[5d5B6UUN3ME2wMlM2QTFzIN88US=> MXPTRW5ITVJ?
ALL-PO NHrKNJlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnvTTWM2OD1yLkixNlc4KM7:TR?= MYXTRW5ITVJ?
SK-LMS-1 NWjke4tqT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVTJR|UxRTBwOEm4OFYh|ryP MonHV2FPT0WU
MV-4-11 M{jFcGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NInodm1KSzVyPUGuNlk1PyEQvF2= M{L4cnNCVkeHUh?=
SUP-T1 NUP6T|hVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2LONWlEPTB;Mj6xN|k3PCEQvF2= M3P3fXNCVkeHUh?=
MRK-nu-1 NHTCblFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYrrXWVPUUN3ME2yMlQxODV4IN88US=> M1ryd3NCVkeHUh?=
ES1 NIjPRnVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmrFTWM2OD1|LkO0PFY3KM7:TR?= NXTlNY5WW0GQR1XS
NOS-1 NITsRpZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYr6NXRLUUN3ME20MlM6QDZ5IN88US=> M1O2cXNCVkeHUh?=
KM12 NFfze|dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVvJR|UxRTRwNEG4JO69VQ>? MnPRV2FPT0WU
Becker NUTPdYE3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFfUXm5KSzVyPUWuNlQ3PiEQvF2= M3vzPHNCVkeHUh?=
NCI-SNU-1 NYHG[JZ1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3T3TWlEPTB;NT62N|c{OyEQvF2= MX3TRW5ITVJ?
EW-22 NHLxRYtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmSzTWM2OD15LkezOlE1KM7:TR?= NHu3R5NUSU6JRWK=
ES6 NUjQZ|BFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXjRdpN{UUN3ME23MlgyQTVizszN MYHTRW5ITVJ?
A498 M2Tm[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV3JR|UxRThwMki0OFYh|ryP M3zpPXNCVkeHUh?=
EW-16 NHnpVIVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mm\6TWM2OD17Lk[1OFMh|ryP MkTCV2FPT0WU
CTV-1 NH;0Wm9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHvBTGZKSzVyPUmuPFUxOjRizszN NXezXmRPW0GQR1XS
ETK-1 MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4LYdGlEPTB;MUCuNlk{OSEQvF2= MVnTRW5ITVJ?
NCI-H1395 NFPsb4xIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{XYdGlEPTB;MUCuPFAzPCEQvF2= MmX0V2FPT0WU
DOHH-2 NWS2WXh3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVrJR|UxRTFyLkmyOlQh|ryP NY\zb2xuW0GQR1XS
GI-1 MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NH7NbpBKSzVyPUGxMlg2QTZizszN NUTLT2RuW0GQR1XS
HT-144 MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4\jVGlEPTB;MUSuNlE3OyEQvF2= NFPSO3pUSU6JRWK=
ES5 MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmDBTWM2OD1zND60Olch|ryP MY\TRW5ITVJ?
NALM-6 NYfvOYV[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFjlSmxKSzVyPUG1MlIyQTZizszN MkfFV2FPT0WU
KNS-81-FD NIHwcYlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{Lld2lEPTB;MUWuOVg1QSEQvF2= NIju[GFUSU6JRWK=
TE-15 NE\uN2hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVjJR|UxRTF4LkW3O|Eh|ryP NYDKPXloW0GQR1XS
SCC-15 MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1\WbWlEPTB;MUiuN|Q6QCEQvF2= Mk\aV2FPT0WU
EoL-1-cell NVPtfXRvT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHL4U2xKSzVyPUG4MlQ2PDVizszN NHnRXFBUSU6JRWK=
NCI-H720 M3S0ZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2XMRmlEPTB;MUiuO|cyKM7:TR?= MYrTRW5ITVJ?
NB14 NUiwbI1wT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHjNPGtKSzVyPUG5MlU1OjVizszN NF7ydopUSU6JRWK=
KE-37 NFS1OWhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3\2TWlEPTB;MUmuPFI{OyEQvF2= NFi0V4lUSU6JRWK=
LXF-289 NFXxb3ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXLJR|UxRTF7Lki2Nlkh|ryP M3PacnNCVkeHUh?=
RPMI-8402 M2DGNGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlPvTWM2OD1{MD6zNlY6KM7:TR?= MWLTRW5ITVJ?
SK-N-DZ NHXM[4VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVm1ToRvUUN3ME2yNU4zOTNzIN88US=> M{XYO3NCVkeHUh?=
ACN NF3kS|NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFvCPZlKSzVyPUKyMlI1QTdizszN NFKzfJpUSU6JRWK=
TE-11 MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{HDWGlEPTB;Mk[uNFY6KM7:TR?= MlzvV2FPT0WU
COLO-800 NE\W[mxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUPxTYppUUN3ME2yO{4yPyEQvF2= MkjrV2FPT0WU
MOLT-13 NUPqdlhsT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3nPfWlEPTB;MkeuNVg1PyEQvF2= MXjTRW5ITVJ?
697 NWj1WmtPT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVXCPJhPUUN3ME2yPE44PjN|IN88US=> NF60N2xUSU6JRWK=
VA-ES-BJ MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlTGTWM2OD1{OT6zO|I6KM7:TR?= NYPxVpU6W0GQR1XS
EW-13 MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M12zcGlEPTB;MkmuOVA1PSEQvF2= NFLWWIZUSU6JRWK=
NB7 M3;1dmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Ml;HTWM2OD1|Mj6yOlY2KM7:TR?= MkHUV2FPT0WU
MONO-MAC-6 NHK2S3pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUWz[lM4UUN3ME2zNk45Pzl3IN88US=> M3;5N3NCVkeHUh?=
SW962 M1;4emdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlLLTWM2OD1|Mz60OVE{KM7:TR?= NFrNNotUSU6JRWK=
KS-1 NHfE[JdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHu2co1KSzVyPUOzMlk1QDFizszN NGPwd|JUSU6JRWK=
KU812 NUDtepVGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVfJdHdwUUN3ME2zOE42PzB{IN88US=> NWG0cYRbW0GQR1XS
IMR-5 MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlTLTWM2OD1|Nz60N|E5KM7:TR?= M4HmVnNCVkeHUh?=
BC-1 MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHHIUFhKSzVyPUO4MlA{OyEQvF2= NVf5T2poW0GQR1XS
NCI-H510A NFHBe5hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2fEOWlEPTB;M{iuNlA{OiEQvF2= MWnTRW5ITVJ?
EW-18 NH3G[pZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4LkOWlEPTB;NECuPFMxOyEQvF2= NH32UoVUSU6JRWK=
CCRF-CEM MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYXJR|UxRTR{LkK3PVch|ryP MlzJV2FPT0WU
HH NXnHTGV1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MorITWM2OD12Mz61NFY6KM7:TR?= NUDBeHR1W0GQR1XS
NCI-H2171 MoDTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1zqcGlEPTB;NE[uNFI4OiEQvF2= MX\TRW5ITVJ?
LC-2-ad NEj3NY1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVnJR|UxRTR7LkG0NVMh|ryP NHP0fGxUSU6JRWK=

... 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

Bio Calculators

Molarity Calculator

Molarity Calculator

Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

  • Mass
    Concentration
    Volume
    Molecular Weight

*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).

Dilution Calculator

Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

Concentration (start) x Volume (start) = Concentration (final) x Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

  • C1
    V1
    C2
    V2

* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).

The Serial Dilution Calculator Equation

  • Serial Dilutions

  • Computed Result

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
Molecular Weight Calculator

Molecular Weight Calculator

Enter the chemical formula of a compound to calculate its molar mass and elemental composition:

Total Molecular Weight: g/mol

Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Molarity Calculator

Mass Concentration Volume Molecular Weight

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.

  • * Indicates a Required Field

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.

c-Met Signaling Pathway Map

c-Met Inhibitors with Unique Features

Related c-Met Products

Tags: buy PHA-665752 | PHA-665752 supplier | purchase PHA-665752 | PHA-665752 cost | PHA-665752 manufacturer | order PHA-665752 | PHA-665752 distributor
×
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID