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)
c-Abl [1]
(Cell-free assay)
FGFR1 [1]
(Cell-free assay)
9 nM 68 nM 200 nM 1.4 μM 3 μM
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 MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWD5[lRjUUN3ME2wMlEzOzd3IN88US=> NYqz[W13W0GQR1XS
LB2241-RCC MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mo\hTWM2OD1yLkG1O|AzKM7:TR?= MXfTRW5ITVJ?
KINGS-1 NH;QOJpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NX\tOGY{UUN3ME2wMlM2QTFzIN88US=> NXPR[WdHW0GQR1XS
ALL-PO NVnMO|lYT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnzXTWM2OD1yLkixNlc4KM7:TR?= M3O4T3NCVkeHUh?=
SK-LMS-1 MlfwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVTJR|UxRTBwOEm4OFYh|ryP MlLTV2FPT0WU
MV-4-11 NFvJTW1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXj5WHJTUUN3ME2xMlI6PDdizszN NVT4[G11W0GQR1XS
SUP-T1 MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4r0e2lEPTB;Mj6xN|k3PCEQvF2= MmC2V2FPT0WU
MRK-nu-1 M{izRWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1W5TmlEPTB;Mj60NFA2PiEQvF2= MmjvV2FPT0WU
ES1 M2fWPWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHf5Z25KSzVyPUOuN|Q5PjZizszN NWTidmQ{W0GQR1XS
NOS-1 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFv5VJJKSzVyPUSuN|k5PjdizszN NWfWeJhMW0GQR1XS
KM12 NIfySJBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M33vZmlEPTB;ND60NVgh|ryP NVmyb5FvW0GQR1XS
Becker M1fQUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NF7NTmFKSzVyPUWuNlQ3PiEQvF2= NEnvPWJUSU6JRWK=
NCI-SNU-1 M1zG[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlTYTWM2OD13Lk[zO|M{KM7:TR?= MXHTRW5ITVJ?
EW-22 NHLk[5pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1HYd2lEPTB;Nz63N|YyPCEQvF2= NV[0bY9NW0GQR1XS
ES6 M3qxUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIfIN5ZKSzVyPUeuPFE6PSEQvF2= M3G1THNCVkeHUh?=
A498 M4mxTWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MonqTWM2OD16LkK4OFQ3KM7:TR?= MX;TRW5ITVJ?
EW-16 M1L6RWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2HVcGlEPTB;OT62OVQ{KM7:TR?= NGjPbJJUSU6JRWK=
CTV-1 MYrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXLafolGUUN3ME25Mlg2ODJ2IN88US=> M1rrRnNCVkeHUh?=
ETK-1 MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MV;JR|UxRTFyLkK5N|Eh|ryP NVHafVM{W0GQR1XS
NCI-H1395 NF3xW2JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXfYRXY1UUN3ME2xNE45ODJ2IN88US=> MnTiV2FPT0WU
DOHH-2 NWr0W5h{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVrXXmFUUUN3ME2xNE46OjZ2IN88US=> MXPTRW5ITVJ?
GI-1 NHTvRXJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXrzO4NXUUN3ME2xNU45PTl4IN88US=> NHLTeWRUSU6JRWK=
HT-144 NIWzVlhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1[wOmlEPTB;MUSuNlE3OyEQvF2= NEfTe3lUSU6JRWK=
ES5 Mnr6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVXJR|UxRTF2LkS2O{DPxE1? M3\BbHNCVkeHUh?=
NALM-6 MnnyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWLJR|UxRTF3LkKxPVYh|ryP MnnQV2FPT0WU
KNS-81-FD M2fM[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIXCbGJKSzVyPUG1MlU5PDlizszN M2HhTXNCVkeHUh?=
TE-15 NVrwTod1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIC4RZBKSzVyPUG2MlU4PzFizszN MlrLV2FPT0WU
SCC-15 NU\ufYpYT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlTuTWM2OD1zOD6zOFk5KM7:TR?= NH2xPYpUSU6JRWK=
EoL-1-cell Mn\rS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWrxbYpRUUN3ME2xPE41PTR3IN88US=> MVTTRW5ITVJ?
NCI-H720 NF\lNJRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlXsTWM2OD1zOD63O|Eh|ryP MVnTRW5ITVJ?
NB14 MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4OweGlEPTB;MUmuOVQzPSEQvF2= Moe2V2FPT0WU
KE-37 Mk\DS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIK0[5dKSzVyPUG5MlgzOzNizszN M1XqVXNCVkeHUh?=
LXF-289 MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVPO[5RYUUN3ME2xPU45PjJ7IN88US=> MVPTRW5ITVJ?
RPMI-8402 MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MY\JR|UxRTJyLkOyOlkh|ryP NYLld|BTW0GQR1XS
SK-N-DZ NUHlVWVJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYrLXVd[UUN3ME2yNU4zOTNzIN88US=> NH3VdpFUSU6JRWK=
ACN MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVnJR|UxRTJ{LkK0PVch|ryP M3XmT3NCVkeHUh?=
TE-11 MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXTHTnA6UUN3ME2yOk4xPjlizszN MUXTRW5ITVJ?
COLO-800 NYq0RY9vT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnvLTWM2OD1{Nz6xO{DPxE1? Mki3V2FPT0WU
MOLT-13 NF\GRnRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUXJR|UxRTJ5LkG4OFch|ryP MlK4V2FPT0WU
697 NFjkUHFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mny1TWM2OD1{OD63OlM{KM7:TR?= NGTnXmpUSU6JRWK=
VA-ES-BJ MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkCzTWM2OD1{OT6zO|I6KM7:TR?= NWPGd2htW0GQR1XS
EW-13 MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHfvXZhKSzVyPUK5MlUxPDVizszN MUDTRW5ITVJ?
NB7 NHvWe3NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2jUfGlEPTB;M{KuNlY3PSEQvF2= NX7wcppRW0GQR1XS
MONO-MAC-6 MmK1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{fn[2lEPTB;M{KuPFc6PSEQvF2= NFrPRmpUSU6JRWK=
SW962 NX7Re3FNT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYfvblhVUUN3ME2zN{41PTF|IN88US=> MYnTRW5ITVJ?
KS-1 MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUDXfWVDUUN3ME2zN{46PDhzIN88US=> M2TYUnNCVkeHUh?=
KU812 NWLxOndHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2\zeWlEPTB;M{SuOVcxOiEQvF2= MXfTRW5ITVJ?
IMR-5 MlnaS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHS5eINKSzVyPUO3MlQ{OThizszN M2q1NnNCVkeHUh?=
BC-1 MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWXMdlF1UUN3ME2zPE4xOzNizszN M17QTnNCVkeHUh?=
NCI-H510A M3zUZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYTJR|UxRTN6LkKwN|Ih|ryP MVHTRW5ITVJ?
EW-18 NV7rN5hYT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGDp[4JKSzVyPUSwMlg{ODNizszN MlnYV2FPT0WU
CCRF-CEM MmT1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{LOXmlEPTB;NEKuNlc6PyEQvF2= NIHZdGdUSU6JRWK=
HH NGizOoVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWPJR|UxRTR|LkWwOlkh|ryP NILDeJVUSU6JRWK=
NCI-H2171 NFL6PFRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWP3UnNlUUN3ME20Ok4xOjd{IN88US=> M3PK[HNCVkeHUh?=
LC-2-ad M3jPWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{jUSmlEPTB;NEmuNVQyOyEQvF2= NXW4Vo0{W0GQR1XS

... 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 slightly soluble or insoluble
Ethanol slightly soluble or 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
in solvent
Synonyms N/A

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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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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID