BMS-777607

Catalog No.S1561

BMS-777607 Chemical Structure

Molecular Weight(MW): 512.89

BMS-777607 is a Met-related inhibitor for c-Met, Axl, Ron and Tyro3 with IC50 of 3.9 nM, 1.1 nM, 1.8 nM and 4.3 nM in cell-free assays, 40-fold more selective for Met-related targets versus Lck, VEGFR-2, and TrkA/B, and more than 500-fold greater selectivity versus all other receptor and non receptor kinases. Phase 1/2.

Size Price Stock Quantity  
In DMSO USD 250 In stock
USD 120 In stock
USD 210 In stock
USD 670 In stock

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6 Customer Reviews

  • Numbers of clonogenic cells from L3.6pl cells and CSCs+24/44/ESAin duplicate were counted. Clonogenic growth from the cell control was set as 100%.

    Mol Cancer Ther 2014 13(1), 37-48. BMS-777607 purchased from Selleck.

    The inhibitory effect of BMS-777607 on survival and proliferation of L3.6pl and CSCs+24/44/ESA was determined by the clonogenic assay. Briefly, L3.6pl cells (6,000 cells/well) in minimum essential media (MEM) with 5% FBS were cultured in duplicate in a 24-well plate and then treated with different amounts of BMS-777607 for 12 days. CSCs+24/44/ESA in stem cell culture media were incubated for 18 days in the ultra-low attachment culture plate coated with a thin layer of 0.2% of agarose to facilitate cell anchored growth. Clonogenic cells were stained with Hema-3 staining solution (Fisher Scientific), photographed using an Olympus BK71 microscope equipped with CCD camera, and counted. The number of clonogenic growth from individual groups is presented.

    Mol Cancer Ther 2014 13(1), 37-48. BMS-777607 purchased from Selleck.

  • Mol Oncol 2013 10.1016/j.molonc.2013.12.014. BMS-777607 purchased from Selleck.

    BMS-777607 increases p21/WAF1 and survivin expression but down-regulates Rb expression. T-47D and ZR-75-1 cells (2×106 cells in 60 mm diameter culture dish) were treated with 5 mM BMS-777607 for different time intervals. Cellular proteins (50 mg per sample) from cell lysates were subjected to Western blot analysis using individual antibodies specific to p53, p21/WAF1, survivin, regular and phospho-Rb. B-actin was used as the loading control.

    Mol Oncol 2013 8, 469-82. BMS-777607 purchased from Selleck.

  • Effect of BMS-777607 on growth and survival of breast cancer cells. A, the effect of BMS-777607 on survival and proliferation of MCF-7, ZR-75-1, and T-47D cells was determined by clonogenic assay. Briefly, cells (8,000 cells per well) in RPMI-1640 with 5% FBS were cultured in duplicate in a 24-well plate and then treated with different amounts of BMS-777607 for 10 days. Clonogenic cells were stained with Hema-3 staining solution (Fisher Scientific) and photographed using an Olympus BK71 microscope equipped with CCD camera. B, numbers of clonogenic cells in duplicate from 3 cell lines were counted.

    Acta Pharmacol Sin 2013 34, 1545-53. BMS-777607 purchased from Selleck.

    Effect of MEK inhibitor BMS-777607 in A549 cells. A549 cells were incubated with increasing concentrations of BMS-777607 for 2 h. The cell lysates were harvested and phosphorylation of indicated proteins was determined by Western blotting.

    2014 Dr.Wang from Southern Medical Hospital. BMS-777607 purchased from Selleck.

Purity & Quality Control

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Notes:

2. For more details, such as half maximal inhibitory concentrations (IC50s) and working concentrations of each inhibitor, please click on the link of the inhibitor of interest.
3. "+" indicates inhibitory effect. Increased inhibition is marked by a higher "+" designation.
4. Orange "√" refers to compounds which do inhibitory effects on the related isoform, but without specific value.

Biological Activity

Description BMS-777607 is a Met-related inhibitor for c-Met, Axl, Ron and Tyro3 with IC50 of 3.9 nM, 1.1 nM, 1.8 nM and 4.3 nM in cell-free assays, 40-fold more selective for Met-related targets versus Lck, VEGFR-2, and TrkA/B, and more than 500-fold greater selectivity versus all other receptor and non receptor kinases. Phase 1/2.
Features A potent inhibitor of the Met family, and >40-fold selectivity vs. Lck, VEGFR2, and TrkA/B and >500-fold selective vs. other receptor and non-receptor kinases.
Targets
Axl [1]
(Cell-free assay)
RON [1]
(Cell-free assay)
Met [1]
(Cell-free assay)
Tyro3 [1]
(Cell-free assay)
Mer [1]
(Cell-free assay)
1.1 nM 1.8 nM 3.9 nM 4.3 nM 14 nM
In vitro

BMS-777607 is a selective ATP-competitive Met kinase inhibitor which potently blocks the autophosphorylation of c-Met with IC50 of 20 nM in GTL-16 cell lysates, and demonstrates selective inhibition of proliferation in Met-driven tumor cell lines, such as GTL-16 cell line, H1993 and U87. [1] BMS-777607 inhibits hepatocyte growth factor (HGF)-triggered c-Met autophosphorylation with IC50 of <1 nM in PC-3 and DU145 prostate cancer cells. BMS 777607 has little effect on tumor cell growth, but exhibits inhibitory effect on HGF-induced cell scattering in PC-3 and DU145 cells, with almost complete inhibition at 0.5 μM. BMS 777607 also suppresses stimulated cell migration and invasion in a dose-dependent fashion (IC50 < 0.1 μM) in both cell lines. [2] Application of BMS 777607 (~10 μM) to the highly metastatic murine KHT cells for 2 hours potently eliminates basal levels of autophosphorylated c-Met with IC50 of 10 nM without affecting the total c-Met, leading to dose-dependent inhibition of phosphorylation of downstream signaling molecules including ERK, Akt, p70S6K and S6. Treatment with BMS-777607 (~1 μM) for 24 hours potently inhibits the KHT cell scatter, motility and invasion at doses in the nanomolar range which consists with MET gene knockdown, and modestly affects cell proliferation and colony formation. [3]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
GTL-16 NVK3NZhjU2mwYYPlJIF{e2G7 NELNWJVFVVOR M{DiS4lvcGmkaYTzJG1mfCCtaX7hd4Uhf2m2aDDJR|UxKG:oIEGwNEBvVQ>? M4PXUVE6OjZyN{Gx
H1993 Ml\sS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl? Mo\IglExKM7:TR?= M1TFN2ROW09? NFHXU3NKSzVyPUG1NEBvVQ>? MVuxPVI3ODdzMR?=
U87 NH60bVhIem:5dHigbY5pcWKrdH;yfUBie3OjeR?= NGXWcHh,OTBizszN NGDSTZlFVVOR NYHKW21HUUN3ME2xOlAhdk1? M{DvS|E6OjZyN{Gx
PC-3 NGfVcVFHfW6ldHnvckBie3OjeR?= NGjyc2UxNjFizszN M4jLfmROW09? MoLM[ZhpcWKrdIOgbY5pcWKrdH;yfUBm\m[nY4Sgc44hUEeILXnu[JVk\WRiY3XscEB{[2G2dHXybY5o M2PrNFIxPTF3OUSz
DU145 NVL4UohLTnWwY4Tpc44h[XO|YYm= M2frVFAvOSEQvF2= NF;veFlFVVOR NYezZWJD\XiqaXLpeJMhcW6qaXLpeI9zgSCnZn\lZ5Qhd25iSFfGMYlv\HWlZXSgZ4VtdCC|Y3H0eIVzcW6p MY[yNFUyPTl2Mx?=
PC-3 M1PkN2Z2dmO2aX;uJIF{e2G7 NX\iSIhqOC5yMTFOwG0> MojhSG1UVw>? MmTod5VxeHKnc4Pld{BJT0ZvaX7keYNm\CClZXzsJI1q\3KjdHnvci=> NUjSXIp4OjB3MUW5OFM>
DU145 MXLGeY5kfGmxbjDhd5NigQ>? MX6wMlAyKM7:TR?= Ml;uSG1UVw>? Mnm5d5VxeHKnc4Pld{BJT0ZvaX7keYNm\CClZXzsJI1q\3KjdHnvci=> MWqyNFUyPTl2Mx?=
PC-3 NVLDRWMxTnWwY4Tpc44h[XO|YYm= MU[wMlEh|ryP MoLoSG1UVw>? MlHhbY1x[Wm{czDIS2YudWWmaXH0[YQh[2WubDDpcpZie2mxbh?= NFTkOFkzODVzNUm0Ny=>
DU145 NFHBOG1HfW6ldHnvckBie3OjeR?= NHywNVYxNjFizszN NGjTfo1FVVOR MVfpcZBicXK|IFjHSk1u\WSrYYTl[EBk\WyuIHnueoF{cW:w Mnm5NlA2OTV7NEO=
PC-3 M4HrVWdzd3e2aDDpcohq[mm2b4L5JIF{e2G7 NX:xeXEzhjFyIN88US=> MYnEUXNQ NGDYZW9z\WS3Y3XzJINmdGxicILvcIln\XKjdHnvci=> NIjLUpozODVzNUm0Ny=>
KHT NGLmRXNMcW6jc3WgZZN{[Xl? MWnEUXNQ NFvR[mtjdG:la4OgeIhmKGNvTXX0JJNq\26jbHnu[{Bx[XSqd3H5JJdqfGhiSVO1NEBw\iBzMDDuUS=> MnWwNlIzQDZ3MkO=
KHT MoHVSpVv[3Srb36gZZN{[Xl? MXr+NUDPxE1? NIj0VGJFVVOR Mm\vdJJmfmWwdIOgd5BwdnSjbnXveZMhU0iWIHPlcIwhe2OjdITldolv\yC5aYToJGlEPTBib3[gNE4yNTBwNTFOwG0> MUmyNlI5PjV{Mx?=
KHT M4TsVGZ2dmO2aX;uJIF{e2G7 NFHyZ25,OC53IN88US=> MUPEUXNQ NED1TVRqdmirYnn0d{Bk\WyuIH3p[5JifGmxbh?= M1XteVIzOjh4NUKz
KHT MkjtSpVv[3Srb36gZZN{[Xl? NHr1SGh,OC53IN88US=> NH;EXpBFVVOR M3\vbYlvcGmkaYTzJINmdGxiaX72ZZNqd25? M4HuUFIzOjh4NUKz
KHT MoX5S5Jwf3SqIHnubIljcXSxcomgZZN{[Xl? M3fkT54yOCEQvF2= MYXEUXNQ MlXhbY5pcWKrdIOgT2hVKGOnbHygdJJwdGmoZYLheIlwdg>? NVfXdYZROjJ{OE[1NlM>
T-47D NIPhem5Iem:5dHigbY5pcWKrdH;yfUBie3OjeR?= NXjFdY9{hjVizszN MkXmSG1UVw>? MXHpcohq[mm2czDj[YxtKHC{b3zp[oVz[XSrb36= M1myXlI{PDZ6NUK5
ZR-75-1 MnzhS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl? NHi1UHJ,PSEQvF2= M{i0V2ROW09? MoH1bY5pcWKrdIOgZ4VtdCCycn;sbYZmemG2aX;u M1zTN|I{PDZ6NUK5
T-47D NF3iVmhHfW6ldHnvckBie3OjeR?= M3TDWVExKM7:TR?= M2L0SGROW09? M1HBdWlv\HWlZYOgdI9tgXCub3nkfUBjgSB6NjCl NG\RdlEzOzR4OEWyPS=>
ZR-75-1 M4nvTGZ2dmO2aX;uJIF{e2G7 MX6xNEDPxE1? MmfySG1UVw>? M1H6W2lv\HWlZYOgdI9tgXCub3nkfUBjgSB6ODW= MVGyN|Q3QDV{OR?=
T-47D MnvzSpVv[3Srb36gZZN{[Xl? MmDLNVAh|ryP M4XlVmROW09? NYPKdVFScW6qaXLpeJMhSVWUSz3CJIZ2dmO2aX;uJIFv\CCrbnT1Z4V{KGm2czDwdo91\WmwIHTl[5Ji\GG2aX;u NFjGZ5QzOzR4OEWyPS=>
CHRF M13uZWZ2dmO2aX;uJIF{e2G7 NXHBZVdsOTBizszN MnnjSG1UVw>? NGnhSHpqdmirYnn0d{Bk\WyuIHTpeol{cW:w NFTLSHAzPTNyNEmwNC=>
HPDE NXfvS5VSTnWwY4Tpc44h[XO|YYm= NIDxNmoyOCEQvF2= NFTIepVFVVOR NUPVboxQ[myxY3vzJINwdnO2aYT1eIl3\SCjY4TpeoF1cW:wIHHu[EBl\WO{ZXHz[YQhSUuWIIPp[45idGmwZx?= MViyOlQ4PzNzNB?=
U118MG MX3LbY5ie2ViYYPzZZk> M2K0PJ4{KM7:TR?= M{TUUWROW09? MXnicI9kc3NiQWjMJJBpd3OyaH;yfYxifGmxbh?= Mn2yNlY5PDh3MkS=
SF126 NYL6XZQ3U2mwYYPlJIF{e2G7 MkPHglMh|ryP NXPxbnRvTE2VTx?= NEnHc5BjdG:la4OgRXhNKHCqb4PwbI9zgWyjdHnvci=> NV\1Sph7OjZ6NEi1NlQ>
U118MG MUnDfZRwgGmlaYT5JIF{e2G7 M3vZXFEzNjVizszN MmPxSG1UVw>? M3PFS4Rm[3KnYYPld{BodGmxbXGgZ4VtdCC4aXHibYxqfHl? NGnndmwzPjh2OEWyOC=>
SF126 M1\pRmN6fG:6aXPpeJkh[XO|YYm= NFTpOIUyOi53IN88US=> MWrEUXNQ MYjk[YNz\WG|ZYOg[4xqd22jIHPlcIwhfmmjYnnsbZR6 M{LDW|I3QDR6NUK0
U118MG M13EWmFxd3C2b4Ppd{Bie3OjeR?= MXixNk42KM7:TR?= NFvoTHBFVVOR Mk\sbY5lfWOnczDncIlwdWFiY3XscEBieG:ydH;zbZM> NVO0NWdnOjZ6NEi1NlQ>
SF126 MnjaRZBweHSxc3nzJIF{e2G7 NHHU[mEyOi53IN88US=> NVnCdo5zTE2VTx?= M4Xneolv\HWlZYOg[4xqd22jIHPlcIwh[XCxcITvd4l{ NUPq[mFKOjZ6NEi1NlQ>
U118MG MlrXSpVv[3Srb36gZZN{[Xl? M4XJVVEzNjVizszN MYTEUXNQ NVvvcWhP[myxY3vzJIdtcW:vYTDj[YxtKG2rZ4LheIlwdiCjbnSgbY53[XOrdnWg[5Jwf3SqIIDheJRmem5? MX6yOlg1QDV{NB?=
SF126 MmHmSpVv[3Srb36gZZN{[Xl? NHrWRngyOi53IN88US=> NEfMV2tFVVOR NYLFZoFs[myxY3vzJIdtcW:vYTDj[YxtKG2rZ4LheIlwdiCjbnSgbY53[XOrdnWg[5Jwf3SqIIDheJRmem5? MkTHNlY5PDh3MkS=

... Click to View More Cell Line Experimental Data

In vivo Oral administration of BMS 777607 (6.25-50 mg/kg) significantly reduces tumor volumes of the GTL-16 human tumor xenografts in athymic mice with no observed toxicity. [1] Administration of BMS 777607 (25 mg/kg/day) decreases the number of KHT lung tumor nodules (28.3%), improves the morphological hemorrhage, and significantly impairs the metastatic phenotype in the 6-8 week-old female C3H/HeJ mice injected with rodent fibrosarcoma KHT cells without apparent systemic toxicity compared to the control treatment. A low dose of BMS 777607 (10 mg/kg) also offers a mild but not significant inhibition of lung nodule formation compared to the vehicle control. [3]

Protocol

Kinase Assay
+ Expand

Met Kinase Assay:

The kinase reaction consists of baculovirus expressed GST-Met, 3 μg of poly(Glu/Tyr), 0.12 μCi 33P γ-ATP, 1 μM ATP in 30 μL of kinase buffer (20 mM Tris-Cl, 5 mM MnCl2, 0.1 mg/mL BSA, 0.5 mM DTT). Reactions are incubated for 1 hour at 30 °C and stopped by the addition of cold trichloroacetic acid (TCA) to a final concentration of 8%. TCA precipitates are collected onto GF/C unifilter plates using a Filtermate universal harvester, and the filters are quantitated using a TopCount 96-well liquid scintillation counter. Dose response curves are generated to determine the concentration required to inhibit 50% of substrate phosphorylation (IC50). BMS 777607 is dissolved at 10 mM in dimethylsulfoxide (DMSO) and evaluated at 10 concentrations, in duplicate.
Cell Research
+ Expand
  • Cell lines: Rodent fibrosarcoma KHT cells
  • Concentrations: Dissolved in DMSO as a stock solution (10 mM), final concentration ~10 μM.
  • Incubation Time: 2, 24 and 96 hours
  • Method: KHT cells are exposed to serial dilution of BMS 777607 for 96 hours, then the MTT assay and trypan blue exclusion are used for the determination of cell proliferation and cell death, respectively. KHT cell colonies are incubated with BMS 777607 for 24 hours and then stained with crystal violet (0.1%) and photographed for the assessment of cell scattering. 2 mm scratch on the confluent KHT cell monolayer is made using a sterilized 1 ml pipette tip followed by treated with BMS-777607 for 24 hours, then the number of cells that have migrated into the denuded area is counted on 4 random fields for the evaluation of cell migration. For the examination of cell invasion, the commercial transwell inserts (8 μm pore membrane) pre-loaded with Matrigel are incubated with serum-free medium in the presence or absence of BMS 777607 at 37 °C for 2 hours to allow rehydration of Matrigel. Then cells suspended in serum-free medium are loaded onto the top chamber (5 × 103/insert) and complete medium (containing 10% FBS) is used in the lower chamber as a chemoattractant. After incubation for 24 hours, the Matrigel is removed and the inserts are stained with crystal violet. Invaded cells on the underside of the filter are photographed and counted.
    (Only for Reference)
Animal Research
+ Expand
  • Animal Models: Rodent fibrosarcoma KHT cells are established in female C3H/HeJ mice.
  • Formulation: Dissolved in DMSO as a stock solution (10 mM).
  • Dosages: 10-25 mg/kg.
  • Administration: Oral gavage once daily.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 47 mg/mL (91.63 mM)
Water <1 mg/mL
Ethanol <1 mg/mL
In vivo 4% DMSO+30% PEG 300+ddH2O 5mg/mL

* 1 mg/ml means slightly soluble or insoluble.
* 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 512.89
Formula

C25H19ClF2N4O4

CAS No. 1025720-94-8
Storage powder
in solvent
Synonyms N/A

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT01721148 Active, not recruiting Malignant Solid Tumour Aslan Pharmaceuticals October 2012 Phase 1
NCT00605618 Completed Advanced Solid Tumors Bristol-Myers Squibb March 2008 Phase 1|Phase 2

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID