BMS-777607

For research use only.

Catalog No.S1561

25 publications

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.

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10mM (1mL in DMSO) USD 250 In stock
USD 120 In stock
USD 210 In stock
USD 670 In stock
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Selleck's BMS-777607 has been cited by 25 publications

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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 NYWzOWtDU2mwYYPlJIF{e2G7 MVjEUXNQ M{K2NolvcGmkaYTzJG1mfCCtaX7hd4Uhf2m2aDDJR|UxKG:oIEGwNEBvVQ>? M2DmVVE6OjZyN{Gx
H1993 MVPHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>? NET5SHJ,OTBizszN NHv4eItFVVOR MnjJTWM2OD1zNUCgcm0> NXz4PG1bOTl{NkC3NVE>
U87 NYLtfHB2T3Kxd4ToJIlvcGmkaYTvdpkh[XO|YYm= MWj+NVAh|ryP MVrEUXNQ MVLJR|UxRTF4MDDuUS=> MVexPVI3ODdzMR?=
PC-3 NYTtfJdTTnWwY4Tpc44h[XO|YYm= M2qyZVAvOSEQvF2= M{jt[2ROW09? MkHR[ZhpcWKrdIOgbY5pcWKrdH;yfUBm\m[nY4Sgc44hUEeILXnu[JVk\WRiY3XscEB{[2G2dHXybY5o MXyyNFUyPTl2Mx?=
DU145 NHHwVIxHfW6ldHnvckBie3OjeR?= M1ToUVAvOSEQvF2= M{O3TmROW09? MlGz[ZhpcWKrdIOgbY5pcWKrdH;yfUBm\m[nY4Sgc44hUEeILXnu[JVk\WRiY3XscEB{[2G2dHXybY5o MUiyNFUyPTl2Mx?=
PC-3 MnLGSpVv[3Srb36gZZN{[Xl? MUmwMlAyKM7:TR?= MXvEUXNQ M4m1SJN2eHC{ZYPz[ZMhUEeILXnu[JVk\WRiY3XscEBucWe{YYTpc44> MUGyNFUyPTl2Mx?=
DU145 MXzGeY5kfGmxbjDhd5NigQ>? M2e0RVAvODFizszN NEjSZXFFVVOR MV7zeZBxemW|c3XzJGhITi2rbnT1Z4VlKGOnbHygcYloemG2aX;u M3zNZVIxPTF3OUSz
PC-3 NV\hN|J1TnWwY4Tpc44h[XO|YYm= MkfqNE4yKM7:TR?= MV\EUXNQ MVfpcZBicXK|IFjHSk1u\WSrYYTl[EBk\WyuIHnueoF{cW:w M2LRfFIxPTF3OUSz
DU145 MnzCSpVv[3Srb36gZZN{[Xl? MWGwMlEh|ryP MWLEUXNQ MnfmbY1x[Wm{czDIS2YudWWmaXH0[YQh[2WubDDpcpZie2mxbh?= NGnHTVMzODVzNUm0Ny=>
PC-3 Ml\5S5Jwf3SqIHnubIljcXSxcomgZZN{[Xl? MVP+NVAh|ryP NET5VIJFVVOR MnnpdoVlfWOnczDj[YxtKHC{b3zp[oVz[XSrb36= MVqyNFUyPTl2Mx?=
KHT MYfLbY5ie2ViYYPzZZk> NF3YVFNFVVOR MlfDZoxw[2u|IITo[UBkNU2ndDDzbYdv[WyrbnegdIF1cHejeTD3bZRpKEmFNUCgc4YhOTBibl2= M4jJRVIzOjh4NUKz
KHT Mk\2SpVv[3Srb36gZZN{[Xl? MmTaglEh|ryP MoP5SG1UVw>? MX3wdoV3\W62czDzdI9vfGGwZX;1d{BMUFRiY3XscEB{[2G2dHXybY5oKHerdHigTWM2OCCxZjCwMlEuOC53IN88US=> NILaPIozOjJ6NkWyNy=>
KHT MmTkSpVv[3Srb36gZZN{[Xl? NVHxW|NnhjBwNTFOwG0> NXL4cXZHTE2VTx?= NYPyS|JmcW6qaXLpeJMh[2WubDDtbYdz[XSrb36= M1zG[VIzOjh4NUKz
KHT NXvxOJA6TnWwY4Tpc44h[XO|YYm= NV;KUolJhjBwNTFOwG0> M3HVOGROW09? MYfpcohq[mm2czDj[YxtKGmwdnHzbY9v MX[yNlI5PjV{Mx?=
KHT MnLsS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl? MnnPglExKM7:TR?= M1XqNmROW09? NGrlT4lqdmirYnn0d{BMUFRiY3XscEBxem:uaX\ldoF1cW:w MXWyNlI5PjV{Mx?=
T-47D NXLjRYFvT3Kxd4ToJIlvcGmkaYTvdpkh[XO|YYm= NWfaPHhLhjVizszN M13kWWROW09? NFLmd3pqdmirYnn0d{Bk\WyuIIDyc4xq\mW{YYTpc44> MVOyN|Q3QDV{OR?=
ZR-75-1 MkjuS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl? NEPjfpB,PSEQvF2= M4nFbWROW09? M4SzbYlvcGmkaYTzJINmdGxicILvcIln\XKjdHnvci=> M4Hu[VI{PDZ6NUK5
T-47D NILZcJJHfW6ldHnvckBie3OjeR?= NYfDO2xKOTBizszN NVq2SYxDTE2VTx?= M3zZSWlv\HWlZYOgdI9tgXCub3nkfUBjgSB6NjCl MWCyN|Q3QDV{OR?=
ZR-75-1 MXrGeY5kfGmxbjDhd5NigQ>? MWCxNEDPxE1? NHPodGJFVVOR NHSyR|NKdmS3Y3XzJJBwdHmybH;p[Jkh[nliOEil NH;wWIYzOzR4OEWyPS=>
T-47D NEHmcItHfW6ldHnvckBie3OjeR?= MUKxNEDPxE1? NGLiU3ZFVVOR Mlz6bY5pcWKrdIOgRXVTUy2EIH\1coN1cW:wIHHu[EBqdmS3Y3XzJIl1eyCycn;0[YlvKGSnZ4Lh[IF1cW:w NYnQPWdlOjN2Nki1Nlk>
CHRF MVXGeY5kfGmxbjDhd5NigQ>? MmjmNVAh|ryP NVHxOYdoTE2VTx?= NYGzblBLcW6qaXLpeJMh[2WubDDkbZZqe2mxbh?= MVKyOVMxPDlyMB?=
HPDE NIXV[4dHfW6ldHnvckBie3OjeR?= M2\TV|ExKM7:TR?= M4HhOmROW09? NXn3dYhv[myxY3vzJINwdnO2aYT1eIl3\SCjY4TpeoF1cW:wIHHu[EBl\WO{ZXHz[YQhSUuWIIPp[45idGmwZx?= M2jvO|I3PDd5M{G0
U118MG MX7LbY5ie2ViYYPzZZk> M1zsU54{KM7:TR?= NWnnTFR7TE2VTx?= MkPzZoxw[2u|IFHYUEBxcG:|cHjvdplt[XSrb36= NH\McFEzPjh2OEWyOC=>
SF126 NWrtTlJHU2mwYYPlJIF{e2G7 NV3UNlh{hjNizszN M4rrTGROW09? NEDBS2ZjdG:la4OgRXhNKHCqb4PwbI9zgWyjdHnvci=> Mlz1NlY5PDh3MkS=
U118MG MnriR5l1d3irY3n0fUBie3OjeR?= MmDaNVIvPSEQvF2= MlrOSG1UVw>? NF;BSpNl\WO{ZXHz[ZMh\2yrb33hJINmdGxidnnhZoltcXS7 M{X6VFI3QDR6NUK0
SF126 NXTaTmIyS3m2b4jpZ4l1gSCjc4PhfS=> NGnSemIyOi53IN88US=> NI\NWZdFVVOR M2LTSIRm[3KnYYPld{BodGmxbXGgZ4VtdCC4aXHibYxqfHl? NYPTW2RNOjZ6NEi1NlQ>
U118MG MV7BdI9xfG:|aYOgZZN{[Xl? M2HEVVEzNjVizszN M4DyV2ROW09? NXPkfoFPcW6mdXPld{BodGmxbXGgZ4VtdCCjcH;weI9{cXN? M2\2bFI3QDR6NUK0
SF126 M1jBc2Fxd3C2b4Ppd{Bie3OjeR?= MlK5NVIvPSEQvF2= M1PvO2ROW09? NF\keVRqdmS3Y3XzJIdtcW:vYTDj[YxtKGGyb4D0c5Nqew>? MYqyOlg1QDV{NB?=
U118MG NVnCNXZxTnWwY4Tpc44h[XO|YYm= MW[xNk42KM7:TR?= M4XtbmROW09? NWTFXpdJ[myxY3vzJIdtcW:vYTDj[YxtKG2rZ4LheIlwdiCjbnSgbY53[XOrdnWg[5Jwf3SqIIDheJRmem5? MoHHNlY5PDh3MkS=
SF126 MoXLSpVv[3Srb36gZZN{[Xl? Mk\HNVIvPSEQvF2= M4H3fmROW09? M3TOTIJtd2OtczDncIlwdWFiY3XscEBucWe{YYTpc44h[W6mIHnueoF{cX[nIHfyc5d1cCCyYYT0[ZJv NWTac3JROjZ6NEi1NlQ>

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
p-c-Met / c-Met / p-FAK / p-c-Src / p-Akt / p-S6K / p-S6; 

PubMed: 22639908     


Effect of BMS-777607 on c-Met signaling in PC-3 cells PC-3 cells were treated with indicated doses of BMS-777607 for 1 h (A) or with BMS-777607 (1 μM) for indicated times (B). Whole cell lysates were harvested and analyzed by Western blot, with actin as a loading control. Data represent 1 of 2 independent experiments.

p53 / p21 / Survivin / p-Rb / Rb ; 

PubMed: 24444656     


BMS-777607 increases p21/WAF1 and survivin expression but down-regulates Rb expression. T-47D and ZR-75-1 cells were treated with 5 μM BMS-777607 for different time intervals. Cellular proteins (50 μg 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.

22639908 24444656
Immunofluorescence
α-tubulin / survivin; 

PubMed: 24444656     


Abnormal accumulation of survivin and its disassociation with condensed DNA and mitotic spindle. Both T-47D and ZR-75-1 cells were treated with 5 μM BMS-777607 for 72 h followed by immunofluorescent analysis using antibodies specific to survivin and α-tubulin. Cells were also stained with DAPI for nuclear DNA. Images shown here are from one of two experiments with similar results.

24444656
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:[4]
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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:[3]
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  • 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:[3]
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  • Animal Models: Rodent fibrosarcoma KHT cells are established in female C3H/HeJ mice.
  • 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 Insoluble
Ethanol Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
4% DMSO+45% PEG 300+5% Tween 80+ddH2O
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 512.89
Formula

C25H19ClF2N4O4

CAS No. 1025720-94-8
Storage powder
in solvent
Synonyms N/A
Smiles CCOC1=C(C(=O)N(C=C1)C2=CC=C(C=C2)F)C(=O)NC3=CC(=C(C=C3)OC4=C(C(=NC=C4)N)Cl)F

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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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Frequently Asked Questions

  • Question 1:

    What formulation can we use to dissolve S1561 for mice in vivo study?

  • Answer:

    S1561 BMS-777607 in 1% DMSO+30% polyethylene glycol+1% Tween 80 at 30 mg/ml is a suspension. It is fine for oral gavage. If you are going to use it for injection, please try the following vehicle: 4% DMSO+30% PEG 300+ddH2O. BMS-777607 can be dissolved in it at 5 mg/ml as a clear solution.

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID