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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Cited by 26 Publications

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 NYP4PGM6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Ml20TWM2OD1yLkGyN|c2KM7:TR?= M1rBcHNCVkeHUh?=
LB2241-RCC MlPJS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkLyTWM2OD1yLkG1O|AzKM7:TR?= MV;TRW5ITVJ?
KINGS-1 MmDmS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFS5OGVKSzVyPUCuN|U6OTFizszN NFXYdpVUSU6JRWK=
ALL-PO MoHrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MU\JR|UxRTBwOEGyO|ch|ryP MnWwV2FPT0WU
SK-LMS-1 NX70PG5LT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3;Zb2lEPTB;MD64PVg1PiEQvF2= M1nyVHNCVkeHUh?=
MV-4-11 MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{\rUWlEPTB;MT6yPVQ4KM7:TR?= NHLlZmZUSU6JRWK=
SUP-T1 MlvlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFzXPJdKSzVyPUKuNVM6PjRizszN NX\jSJM3W0GQR1XS
MRK-nu-1 NVXDNIprT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH;iXllKSzVyPUKuOFAxPTZizszN M3\iR3NCVkeHUh?=
ES1 MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVrpUJJnUUN3ME2zMlM1QDZ4IN88US=> MnvSV2FPT0WU
NOS-1 MkXkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUHJR|UxRTRwM{m4Olch|ryP MVHTRW5ITVJ?
KM12 NFrVO2lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWDJR|UxRTRwNEG4JO69VQ>? NVPS[XZRW0GQR1XS
Becker NGjjRYlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUjJR|UxRTVwMkS2OkDPxE1? MnfSV2FPT0WU
NCI-SNU-1 MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MULJR|UxRTVwNkO3N|Mh|ryP Mk\qV2FPT0WU
EW-22 MoPES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1zLW2lEPTB;Nz63N|YyPCEQvF2= Mlf5V2FPT0WU
ES6 MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlPQTWM2OD15LkixPVUh|ryP MWXTRW5ITVJ?
A498 M2XhUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYDqNmR3UUN3ME24MlI5PDR4IN88US=> NIPHXGZUSU6JRWK=
EW-16 NECwZW5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEHBcG1KSzVyPUmuOlU1OyEQvF2= Mm\wV2FPT0WU
CTV-1 Mnn3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWr0Snl[UUN3ME25Mlg2ODJ2IN88US=> M{jITHNCVkeHUh?=
ETK-1 MlvxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXvVO4tjUUN3ME2xNE4zQTNzIN88US=> NFvMN5JUSU6JRWK=
NCI-H1395 NFWyXWpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MofkTWM2OD1zMD64NFI1KM7:TR?= MWDTRW5ITVJ?
DOHH-2 NG\Fb|BIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnzaTWM2OD1zMD65NlY1KM7:TR?= MX;TRW5ITVJ?
GI-1 MnTQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVvsPGhPUUN3ME2xNU45PTl4IN88US=> NHPCdXFUSU6JRWK=
HT-144 M2jjSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlW0TWM2OD1zND6yNVY{KM7:TR?= MV\TRW5ITVJ?
ES5 NXjPbGppT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXnk[2NnUUN3ME2xOE41PjdizszN NHLVOo9USU6JRWK=
NALM-6 NWX0OFFHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX\LcW94UUN3ME2xOU4zOTl4IN88US=> MYnTRW5ITVJ?
KNS-81-FD NH\nbXRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFWxenpKSzVyPUG1MlU5PDlizszN MV\TRW5ITVJ?
TE-15 MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYPmUG1[UUN3ME2xOk42PzdzIN88US=> NXrVOI9FW0GQR1XS
SCC-15 NI\F[2NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3H3RWlEPTB;MUiuN|Q6QCEQvF2= NWXvbWhOW0GQR1XS
EoL-1-cell MoCyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGjPbpRKSzVyPUG4MlQ2PDVizszN MknNV2FPT0WU
NCI-H720 NYrOV3R[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MX7JR|UxRTF6Lke3NUDPxE1? NIPwXolUSU6JRWK=
NB14 MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlSxTWM2OD1zOT61OFI2KM7:TR?= NYTk[ZV{W0GQR1XS
KE-37 MnP3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlvmTWM2OD1zOT64NlM{KM7:TR?= NILzZZJUSU6JRWK=
LXF-289 NXi0Zm9oT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEexT5JKSzVyPUG5Mlg3OjlizszN NWrRTGRwW0GQR1XS
RPMI-8402 MkW3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHXZXmFKSzVyPUKwMlMzPjlizszN NE\ifJhUSU6JRWK=
SK-N-DZ NIXJclBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWPlbGtLUUN3ME2yNU4zOTNzIN88US=> NV31boY5W0GQR1XS
ACN MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3ziTWlEPTB;MkKuNlQ6PyEQvF2= NUK2c2Z1W0GQR1XS
TE-11 NXXjUVA6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWnIdWR6UUN3ME2yOk4xPjlizszN M3jrVHNCVkeHUh?=
COLO-800 NHXNRZpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4fjdGlEPTB;MkeuNVch|ryP M4PFfXNCVkeHUh?=
MOLT-13 NX;ST5NTT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGTwe2NKSzVyPUK3MlE5PDdizszN NUP3R3NTW0GQR1XS
697 NWTGTnJUT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIOxdodKSzVyPUK4Mlc3OzNizszN MojzV2FPT0WU
VA-ES-BJ NI\PTlFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmroTWM2OD1{OT6zO|I6KM7:TR?= NUjjXXlSW0GQR1XS
EW-13 NUfQcoN{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWXEbodkUUN3ME2yPU42ODR3IN88US=> M4fzWHNCVkeHUh?=
NB7 M3P2Wmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4Tub2lEPTB;M{KuNlY3PSEQvF2= MX;TRW5ITVJ?
MONO-MAC-6 MlixS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml73TWM2OD1|Mj64O|k2KM7:TR?= NGrIOYFUSU6JRWK=
SW962 MmD4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MknYTWM2OD1|Mz60OVE{KM7:TR?= MXjTRW5ITVJ?
KS-1 MmHCS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHnnR5RKSzVyPUOzMlk1QDFizszN M4jUV3NCVkeHUh?=
KU812 M2n3OGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWPqT21KUUN3ME2zOE42PzB{IN88US=> MoS2V2FPT0WU
IMR-5 M4fycmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWPJR|UxRTN5LkSzNVgh|ryP MXrTRW5ITVJ?
BC-1 Mkj4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYLJR|UxRTN6LkCzN{DPxE1? MVzTRW5ITVJ?
NCI-H510A MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFzm[INKSzVyPUO4MlIxOzJizszN MXfTRW5ITVJ?
EW-18 M{ezNWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmnRTWM2OD12MD64N|A{KM7:TR?= MVrTRW5ITVJ?
CCRF-CEM M4HSdGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mmj5TWM2OD12Mj6yO|k4KM7:TR?= M2HBcXNCVkeHUh?=
HH M{DJVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3vVbGlEPTB;NEOuOVA3QSEQvF2= NFTQ[ZFUSU6JRWK=
NCI-H2171 MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NH\4T4NKSzVyPUS2MlAzPzJizszN MXHTRW5ITVJ?
LC-2-ad NWjScHlYT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M13VPGlEPTB;NEmuNVQyOyEQvF2= MmHJV2FPT0WU

... 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