BMS-777607

製品コードS1561

BMS-777607化学構造

分子量(MW):512.89

BMS-777607は一種のMet関連の阻害剤で、無細胞実験でc-Met、Axl、RonとTyro3に作用する時のIC50値が3.9 nM、1.1 nM、1.8 nMと4.3 nMにそれぞれ分かれることです。BMS-777607は、Met関連ターゲットに作用する選択性はLck、VEGFR-2とTrkA/Bに作用する選択性より40倍が高くなって、他の受容体と非受容体のキナーゼに作用する選択性より500倍が高くなります。臨床 1/2期。

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カスタマーフィードバック(6)

  • 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.

製品安全説明書

c-Met阻害剤の選択性比較

生物活性

製品説明 BMS-777607は一種のMet関連の阻害剤で、無細胞実験でc-Met、Axl、RonとTyro3に作用する時のIC50値が3.9 nM、1.1 nM、1.8 nMと4.3 nMにそれぞれ分かれることです。BMS-777607は、Met関連ターゲットに作用する選択性はLck、VEGFR-2とTrkA/Bに作用する選択性より40倍が高くなって、他の受容体と非受容体のキナーゼに作用する選択性より500倍が高くなります。臨床 1/2期。
特性 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.
靶点
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試験

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 MlXOT4lv[XOnIHHzd4F6 MnrDSG1UVw>? MoTkbY5pcWKrdIOgUYV1KGurbnHz[UB4cXSqIFnDOVAhd2ZiMUCwJI5O NWW5ZohwOTl{NkC3NVE>
H1993 MkjIS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl? NWPnXJFrhjFyIN88US=> M2XqdWROW09? NEnrfJFKSzVyPUG1NEBvVQ>? NXfQUJlZOTl{NkC3NVE>
U87 NYTlO4NzT3Kxd4ToJIlvcGmkaYTvdpkh[XO|YYm= NX7RUm57hjFyIN88US=> NFHLfVlFVVOR MYfJR|UxRTF4MDDuUS=> MVGxPVI3ODdzMR?=
PC-3 MYHGeY5kfGmxbjDhd5NigQ>? M162OVAvOSEQvF2= MUfEUXNQ M2rucIV5cGmkaYTzJIlvcGmkaYTvdpkh\W[oZXP0JI9vKEiJRj3pcoR2[2WmIHPlcIwhe2OjdITldolv\w>? NUTBeYVWOjB3MUW5OFM>
DU145 M2TrXmZ2dmO2aX;uJIF{e2G7 NWTXWI5{OC5zIN88US=> Mn3SSG1UVw>? M{S5doV5cGmkaYTzJIlvcGmkaYTvdpkh\W[oZXP0JI9vKEiJRj3pcoR2[2WmIHPlcIwhe2OjdITldolv\w>? MmfWNlA2OTV7NEO=
PC-3 MV\GeY5kfGmxbjDhd5NigQ>? NIjoWWExNjBzIN88US=> MYPEUXNQ M1XRXZN2eHC{ZYPz[ZMhUEeILXnu[JVk\WRiY3XscEBucWe{YYTpc44> MW[yNFUyPTl2Mx?=
DU145 MlHISpVv[3Srb36gZZN{[Xl? M1TY[FAvODFizszN MmX5SG1UVw>? M3TjNJN2eHC{ZYPz[ZMhUEeILXnu[JVk\WRiY3XscEBucWe{YYTpc44> MYmyNFUyPTl2Mx?=
PC-3 MWHGeY5kfGmxbjDhd5NigQ>? NV;t[|M5OC5zIN88US=> MUHEUXNQ NWriSHdFcW2yYXnyd{BJT0ZvbXXkbYF1\WRiY3XscEBqdn[jc3nvci=> NGHkR3YzODVzNUm0Ny=>
DU145 MYLGeY5kfGmxbjDhd5NigQ>? NUKzNmVjOC5zIN88US=> MXfEUXNQ M1jHW4lueGGrcoOgTGdHNW2nZHnheIVlKGOnbHygbY53[XOrb36= M4iyV|IxPTF3OUSz
PC-3 MXTHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>? MkjqglExKM7:TR?= M{ezTWROW09? M{i1ZpJm\HWlZYOgZ4VtdCCycn;sbYZmemG2aX;u MlvhNlA2OTV7NEO=
KHT MnX4T4lv[XOnIHHzd4F6 NIHPO4ZFVVOR NEHOXWtjdG:la4OgeIhmKGNvTXX0JJNq\26jbHnu[{Bx[XSqd3H5JJdqfGhiSVO1NEBw\iBzMDDuUS=> MonaNlIzQDZ3MkO=
KHT NIj3d2ZHfW6ldHnvckBie3OjeR?= MUH+NUDPxE1? M{XvdGROW09? NYLu[nhOeHKndnXueJMhe3CxboThcoVwfXNiS1jUJINmdGxic3PheJRmemmwZzD3bZRpKEmFNUCgc4YhOC5zLUCuOUDPxE1? NF34dGEzOjJ6NkWyNy=>
KHT Ml7JSpVv[3Srb36gZZN{[Xl? MoTxglAvPSEQvF2= NFjMXGlFVVOR NVXW[3d3cW6qaXLpeJMh[2WubDDtbYdz[XSrb36= M4nCZlIzOjh4NUKz
KHT NYXBeZpZTnWwY4Tpc44h[XO|YYm= Mn\jglAvPSEQvF2= M3X4RWROW09? MWjpcohq[mm2czDj[YxtKGmwdnHzbY9v NETnbZEzOjJ6NkWyNy=>
KHT M1rRd2dzd3e2aDDpcohq[mm2b4L5JIF{e2G7 NV\qdoV7hjFyIN88US=> NYjpTYFxTE2VTx?= MYnpcohq[mm2czDLTHQh[2WubDDwdo9tcW[ncnH0bY9v NGPscI8zOjJ6NkWyNy=>
T-47D NX;0VlNZT3Kxd4ToJIlvcGmkaYTvdpkh[XO|YYm= Mlv3glUh|ryP NELvcHVFVVOR MnrWbY5pcWKrdIOgZ4VtdCCycn;sbYZmemG2aX;u MmDHNlM1Pjh3Mkm=
ZR-75-1 M4PSU2dzd3e2aDDpcohq[mm2b4L5JIF{e2G7 M4DOcZ42KM7:TR?= MV3EUXNQ MX\pcohq[mm2czDj[YxtKHC{b3zp[oVz[XSrb36= NEPKb|EzOzR4OEWyPS=>
T-47D MX3GeY5kfGmxbjDhd5NigQ>? NGKx[ZoyOCEQvF2= NX\EbVVZTE2VTx?= NHm4c3pKdmS3Y3XzJJBwdHmybH;p[Jkh[nliOE[gKS=> NF;MXnQzOzR4OEWyPS=>
ZR-75-1 Mo[zSpVv[3Srb36gZZN{[Xl? NHi0OpYyOCEQvF2= NI\rT4hFVVOR NV7JWo5uUW6mdXPld{Bxd2y7cHzvbYR6KGK7IEi4KS=> NV3PdYtROjN2Nki1Nlk>
T-47D NVLyfZA3TnWwY4Tpc44h[XO|YYm= NWXZ[llQOTBizszN MWfEUXNQ NYm5eWxrcW6qaXLpeJMhSVWUSz3CJIZ2dmO2aX;uJIFv\CCrbnT1Z4V{KGm2czDwdo91\WmwIHTl[5Ji\GG2aX;u MY[yN|Q3QDV{OR?=
CHRF MmflSpVv[3Srb36gZZN{[Xl? M4Cze|ExKM7:TR?= MnrwSG1UVw>? Mly4bY5pcWKrdIOgZ4VtdCCmaY\pd4lwdg>? MVuyOVMxPDlyMB?=
HPDE NHHVfpFHfW6ldHnvckBie3OjeR?= Mn;KNVAh|ryP NVS1RppOTE2VTx?= MUnicI9kc3NiY3;ud5RqfHW2aY\lJIFkfGm4YYTpc44h[W6mIHTlZ5Jm[XOnZDDBT3Qhe2mpbnHsbY5o NFq2[28zPjR5N{OxOC=>
U118MG M2OyOGtqdmG|ZTDhd5NigQ>? MX3+N{DPxE1? NU\GWoxWTE2VTx?= MoCzZoxw[2u|IFHYUEBxcG:|cHjvdplt[XSrb36= MknONlY5PDh3MkS=
SF126 NYrkUXFiU2mwYYPlJIF{e2G7 MUP+N{DPxE1? MlXkSG1UVw>? NYiwWIlC[myxY3vzJGFZVCCyaH;zdIhwenmuYYTpc44> NFXGUIkzPjh2OEWyOC=>
U118MG MVHDfZRwgGmlaYT5JIF{e2G7 MXqxNk42KM7:TR?= M4G4Z2ROW09? MmHU[IVkemWjc3XzJIdtcW:vYTDj[YxtKH[rYXLpcIl1gQ>? MYGyOlg1QDV{NB?=
SF126 NXvFWoZbS3m2b4jpZ4l1gSCjc4PhfS=> MWqxNk42KM7:TR?= NH3senNFVVOR MX\k[YNz\WG|ZYOg[4xqd22jIHPlcIwhfmmjYnnsbZR6 MX:yOlg1QDV{NB?=
U118MG MULBdI9xfG:|aYOgZZN{[Xl? M1rSelEzNjVizszN NFG5WFdFVVOR MWnpcoR2[2W|IHfsbY9u[SClZXzsJIFxd3C2b4Ppdy=> M{DJeVI3QDR6NUK0
SF126 MlTVRZBweHSxc3nzJIF{e2G7 MUOxNk42KM7:TR?= Mnv3SG1UVw>? MXPpcoR2[2W|IHfsbY9u[SClZXzsJIFxd3C2b4Ppdy=> MWGyOlg1QDV{NB?=
U118MG Ml7xSpVv[3Srb36gZZN{[Xl? MY[xNk42KM7:TR?= NXjDWXdQTE2VTx?= NWr6OWdx[myxY3vzJIdtcW:vYTDj[YxtKG2rZ4LheIlwdiCjbnSgbY53[XOrdnWg[5Jwf3SqIIDheJRmem5? MYKyOlg1QDV{NB?=
SF126 NI\lUIlHfW6ldHnvckBie3OjeR?= M1L2cVEzNjVizszN MUfEUXNQ M4j3bYJtd2OtczDncIlwdWFiY3XscEBucWe{YYTpc44h[W6mIHnueoF{cX[nIHfyc5d1cCCyYYT0[ZJv NXHiOXIyOjZ6NEi1NlQ>

... Click to View More Cell Line Experimental Data

In vivo試験 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]

プロトコル(参考用のみ)

キナーゼアッセイ:[4]
+ 展開

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.
細胞アッセイ: [3]
+ 展開
  • 細胞株: Rodent fibrosarcoma KHT cells
  • 濃度: Dissolved in DMSO as a stock solution (10 mM), final concentration ~10 μM.
  • 反応時間: 2, 24 and 96 hours
  • 実験の流れ: 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.
    (参考用のみ)
動物実験:[3]
+ 展開
  • 動物モデル: Rodent fibrosarcoma KHT cells are established in female C3H/HeJ mice.
  • 製剤: Dissolved in DMSO as a stock solution (10 mM).
  • 投薬量: 10-25 mg/kg.
  • 投与方法: Oral gavage once daily.
    (参考用のみ)

溶解度 (25°C)

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

* <1 mg/mlは製品が微弱に溶解する或いは溶解しないことを示します。
* 溶解度検測はSelleck技術部門によって行いますので、文献より提供された溶解度と差異がある可能性がありますが、生産工芸と不同ロット(lot)で起きる正常な現象ですから、ご安心ください。

化学情報

分子量 512.89
化学式

C25H19ClF2N4O4

CAS No. 1025720-94-8
保管
in solvent
別名 N/A

便利ツール

モル濃度計算器

モル濃度計算器

解決のために必要とされるマス、ボリュームまたは濃度を計算してください。

マス (g) = 濃度 (mol/L) x ボリューム (L) x 分子量 (g/mol)

モル濃度計算器方程式

  • マス
    濃度
    ボリューム
    分子量

*貯蔵液を準備するとき、常に、オンであるとわかる製品のバッチに特有の分子量を使って、を通してラベルとMSDS/COA(製品ページで利用可能な)。

希釈計算器

希釈計算器

貯蔵液を準備することを要求される希釈剤を計算してください. セレック希釈計算器は、以下の方程式に基づきます:

開始濃度 x 開始体積 = 最終濃度 x 最終体積

希釈の計算式

この方程式は、一般に略語を使われます:C1V1 = C2V2 ( 輸入 輸出 )

  • C1
    V1
    C2
    V2

常に貯蔵液を準備するとき、小びんラベルとMSDS/COA(オンラインで利用できる)で見つかる製品のバッチに特有の分子量を使ってください。

連続希釈計算器方程式

  • 連続希釈剤

  • 計算結果

  • 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):
分子量計算器

分子量计算器

そのモル質量と元素組成を計算するために、合成物の化学式を入力してください:

総分子量:g/mol

チップス: 化学式は大文字と小文字の区別ができます。C10H16N2O2 c10h16n2o2

モル濃度計算器

マス 濃度 ボリューム 分子量

臨床試験

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT01721148 Completed Malignant Solid Tumour Aslan Pharmaceuticals October 2012 Phase 1
NCT00605618 Completed Advanced Solid Tumors Bristol-Myers Squibb March 2008 Phase 1|Phase 2

技術サポート

ストックの作り方、阻害剤の保管する方法、細胞実験や動物実験に注意すべきな点を全部含めており、製品を取扱う時よくあった質問に対して取扱説明書でお答えいたします。

Handling Instructions

他の質問がある場合は、お気軽くお問合せください。

  • * 必須

c-Met信号経路図

c-Met Inhibitors with Unique Features

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID