BMS-777607

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。

価格 在庫  
USD 151 あり
USD 264 あり
USD 315 あり
USD 844 あり

BMS-777607 化学構造
分子量: 512.89

高品質保証

カスタマーフィードバック(6)

MSDS

製品説明

  • Compare c-Met Inhibitors
    c-Met製品生物活性の比較
  • 研究分野
  • BMS-777607のメカニズム

製品の説明

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。
ターゲット c-Met Axl Ron Tyro3
IC50 3.9 nM 1.1 nM 1.8 nM 4.3 nM [1]
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 LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
GTL-16 M36xcmtqdmG|ZTDhd5NigQ>? MoGySG1UVw>? NUDYZmFbcW6qaXLpeJMhVWW2IHvpcoF{\SC5aYToJGlEPTBib3[gNVAxKG6P NIjBRZUyQTJ4MEexNS=>
H1993 NXnaZZk5T3Kxd4ToJIlvcGmkaYTvdpkh[XO|YYm= M1v6W54yOCEQvF2= NWfud49pTE2VTx?= MUTJR|UxRTF3MDDuUS=> MXmxPVI3ODdzMR?=
U87 MonOS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl? MnLpglExKM7:TR?= M3G3XmROW09? MlXRTWM2OD1zNkCgcm0> M1H6[FE6OjZyN{Gx
PC-3 NEHyNWlHfW6ldHnvckBie3OjeR?= NGntZ|cxNjFizszN NHrH[HlFVVOR NVS4PFVH\XiqaXLpeJMhcW6qaXLpeI9zgSCnZn\lZ5Qhd25iSFfGMYlv\HWlZXSgZ4VtdCC|Y3H0eIVzcW6p MnW0NlA2OTV7NEO=
DU145 MoHGSpVv[3Srb36gZZN{[Xl? NGPKXHgxNjFizszN NVz5[3IxTE2VTx?= MV\lfIhq[mm2czDpcohq[mm2b4L5JIVn\mWldDDvckBJT0ZvaX7keYNm\CClZXzsJJNk[XS2ZYLpcoc> M1XVfFIxPTF3OUSz
PC-3 MVrGeY5kfGmxbjDhd5NigQ>? M4DZdlAvODFizszN MVjEUXNQ MkTHd5VxeHKnc4Pld{BJT0ZvaX7keYNm\CClZXzsJI1q\3KjdHnvci=> M2fMW|IxPTF3OUSz
DU145 NGnofmpHfW6ldHnvckBie3OjeR?= MkCxNE4xOSEQvF2= MVLEUXNQ MVzzeZBxemW|c3XzJGhITi2rbnT1Z4VlKGOnbHygcYloemG2aX;u NILJenQzODVzNUm0Ny=>
PC-3 MVXGeY5kfGmxbjDhd5NigQ>? Mn;oNE4yKM7:TR?= MXLEUXNQ MnjFbY1x[Wm{czDIS2YudWWmaXH0[YQh[2WubDDpcpZie2mxbh?= MnfBNlA2OTV7NEO=
DU145 MlzCSpVv[3Srb36gZZN{[Xl? NWDTSo5NOC5zIN88US=> NFnj[VNFVVOR Ml;hbY1x[Wm{czDIS2YudWWmaXH0[YQh[2WubDDpcpZie2mxbh?= M2Owb|IxPTF3OUSz
PC-3 MkDMS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl? MYH+NVAh|ryP M{ntU2ROW09? NF\lclFz\WS3Y3XzJINmdGxicILvcIln\XKjdHnvci=> NYPVblN6OjB3MUW5OFM>
KHT M2HmZ2tqdmG|ZTDhd5NigQ>? MUfEUXNQ NWTuNmJ[[myxY3vzJJRp\SClLV3leEB{cWewYXzpcocheGG2aIfhfUB4cXSqIFnDOVAhd2ZiMUCgcm0> NH7YRpUzOjJ6NkWyNy=>
KHT NEj4U5NHfW6ldHnvckBie3OjeR?= MkjKglEh|ryP NEj2fXlFVVOR NIniNopxemW4ZX70d{B{eG:wdHHu[Y92eyCNSGSgZ4VtdCC|Y3H0eIVzcW6pIIfpeIghUUN3MDDv[kAxNjFvMD61JO69VQ>? MYWyNlI5PjV{Mx?=
KHT Mlv0SpVv[3Srb36gZZN{[Xl? NW\Uc|RZhjBwNTFOwG0> NYnSeJhTTE2VTx?= MWHpcohq[mm2czDj[YxtKG2rZ4LheIlwdg>? NVTVN2NQOjJ{OE[1NlM>
KHT MoXpSpVv[3Srb36gZZN{[Xl? MXv+NE42KM7:TR?= M{HOT2ROW09? NFnVdXpqdmirYnn0d{Bk\WyuIHnueoF{cW:w MVGyNlI5PjV{Mx?=
KHT M{fmVmdzd3e2aDDpcohq[mm2b4L5JIF{e2G7 M1LSTp4yOCEQvF2= M1;NSGROW09? NF;HSJRqdmirYnn0d{BMUFRiY3XscEBxem:uaX\ldoF1cW:w MnvXNlIzQDZ3MkO=
T-47D M2n3dmdzd3e2aDDpcohq[mm2b4L5JIF{e2G7 M4KzNJ42KM7:TR?= M1zacmROW09? M1vXdYlvcGmkaYTzJINmdGxicILvcIln\XKjdHnvci=> MnjJNlM1Pjh3Mkm=
ZR-75-1 M{DpcWdzd3e2aDDpcohq[mm2b4L5JIF{e2G7 MnLCglUh|ryP MnntSG1UVw>? NULLNpA2cW6qaXLpeJMh[2WubDDwdo9tcW[ncnH0bY9v MXyyN|Q3QDV{OR?=
T-47D MoDUSpVv[3Srb36gZZN{[Xl? NWjjb4QxOTBizszN NHLRT29FVVOR NWHDPY9lUW6mdXPld{Bxd2y7cHzvbYR6KGK7IEi2JEU> MmLUNlM1Pjh3Mkm=
ZR-75-1 M2rIUmZ2dmO2aX;uJIF{e2G7 NHv1UnYyOCEQvF2= MmDzSG1UVw>? NGm4TJlKdmS3Y3XzJJBwdHmybH;p[Jkh[nliOEil NXLmdlRZOjN2Nki1Nlk>
T-47D Mn;mSpVv[3Srb36gZZN{[Xl? MYmxNEDPxE1? MXrEUXNQ NYLkPHNycW6qaXLpeJMhSVWUSz3CJIZ2dmO2aX;uJIFv\CCrbnT1Z4V{KGm2czDwdo91\WmwIHTl[5Ji\GG2aX;u NWjwdVR{OjN2Nki1Nlk>
CHRF MknVSpVv[3Srb36gZZN{[Xl? M{LyUFExKM7:TR?= NGK2[FdFVVOR M3eyOIlvcGmkaYTzJINmdGxiZHn2bZNqd25? Mo\uNlU{ODR7MEC=
HPDE MlLQSpVv[3Srb36gZZN{[Xl? NX;1RoVFOTBizszN NV22bFVLTE2VTx?= NXz0U2dV[myxY3vzJINwdnO2aYT1eIl3\SCjY4TpeoF1cW:wIHHu[EBl\WO{ZXHz[YQhSUuWIIPp[45idGmwZx?= Mmq5NlY1Pzd|MUS=
U118MG NIrXZZVMcW6jc3WgZZN{[Xl? NXG3SIZ4hjNizszN MnvMSG1UVw>? MnrvZoxw[2u|IFHYUEBxcG:|cHjvdplt[XSrb36= Ml;xNlY5PDh3MkS=
SF126 NXn1V5F3U2mwYYPlJIF{e2G7 NHnsNHB,OyEQvF2= NX3NSWVXTE2VTx?= M4C4ZoJtd2OtczDBXGwheGixc4Doc5J6dGG2aX;u M4XUTVI3QDR6NUK0
U118MG MVnDfZRwgGmlaYT5JIF{e2G7 NVnzOWJnOTJwNTFOwG0> MY\EUXNQ M1jJV4Rm[3KnYYPld{BodGmxbXGgZ4VtdCC4aXHibYxqfHl? NYiwNZdbOjZ6NEi1NlQ>
SF126 M4\JTWN6fG:6aXPpeJkh[XO|YYm= MXixNk42KM7:TR?= NGDLSXZFVVOR NGHtRXNl\WO{ZXHz[ZMh\2yrb33hJINmdGxidnnhZoltcXS7 NITFZWYzPjh2OEWyOC=>
U118MG NF;xbnNCeG:ydH;zbZMh[XO|YYm= Mmr1NVIvPSEQvF2= M4GyXWROW09? M4Pyeolv\HWlZYOg[4xqd22jIHPlcIwh[XCxcITvd4l{ MVqyOlg1QDV{NB?=
SF126 NXiwN5hMSXCxcITvd4l{KGG|c3H5 M4C4WlEzNjVizszN M1vpUWROW09? MXjpcoR2[2W|IHfsbY9u[SClZXzsJIFxd3C2b4Ppdy=> NXLEb|ZROjZ6NEi1NlQ>
U118MG MUDGeY5kfGmxbjDhd5NigQ>? NV;zZoFbOTJwNTFOwG0> Mn\MSG1UVw>? MoDRZoxw[2u|IHfsbY9u[SClZXzsJI1q\3KjdHnvckBidmRiaX72ZZNqfmViZ4Lve5RpKHCjdITldo4> NWr6dpV[OjZ6NEi1NlQ>
SF126 MnHaSpVv[3Srb36gZZN{[Xl? NUTwdIk4OTJwNTFOwG0> MnnISG1UVw>? MVricI9kc3NiZ3zpc41iKGOnbHygcYloemG2aX;uJIFv\CCrbo\hd4l3\SCpcn;3eIgheGG2dHXyci=> NEjPd|MzPjh2OEWyOC=>

... 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]
臨床試験 Phase I/II has been completed in the study to find the maximum tolerated dose and the preliminary activity of BMS-777607 in subjects with advanced or metastatic solid tumors, hormone refractory prostate cancer, head and neck squamous cell carcinoma, and t
特集 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.

プロトコル (参考用のみ)

キナーゼアッセイ: [4]

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]

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.

動物実験: [3]

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.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDogMonkeyBaboon
Weight (kg)0.020.151.80.40.0810312
Body Surface Area (m2)0.0070.0250.150.050.020.50.240.6
Km factor361285201220
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

参考

化学情報

Download BMS-777607 SDF
分子量 512.89
化学式

C25H19ClF2N4O4

CAS No. 1025720-94-8
保管 3年-20℃
2年-80℃in solvent
別名 N/A
溶解度 (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.
化学名 N-(4-(2-amino-3-chloropyridin-4-yloxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide

文献中の引用 (9)

技術サポート&よくある質問(FAQ)

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。

電話番号: +1-832-582-8158 Ext:3月曜日〜金曜日 9:00 AM–5:00 PM (米国中部標準時)

他の質問がある場合は、お気軽くお問合せください。

* 必須

Related c-Met 阻害剤

  • NPS-1034は一種の二重Met/Axl阻害剤で、IC50値が48 nMと10.3 nMです。

  • Erlotinib

    Erlotinibは一種のEGFR阻害剤で、このIC50値が2 nMです。Erlotinibは、EGFRに対する敏感性は人間c-Src或いはv-Abに対する敏感性より1000倍以上が高くなります。

  • R428 (BGB324)

    R428 (BGB324)は一種のAxl阻害剤で、IC50値が14 nMです。R428 (BGB324)は、Axlに作用する選択性はAblに作用する選択性より100倍以上が高くなって、MerとTyro3に作用する選択性より50倍-100倍が高くなって、InsR、EGFR、HER2とPDGFRβに作用する選択性より100倍余りが高くなります。

  • Pexidartinib (PLX3397)

    Pexidartinib (PLX3397)は一種の経口有効な多ターゲットCSF-1R、KitとFlt3受容体チロシンキナーゼ阻害剤で、IC50値が20 nM、10 nMと160 nMにそれぞれ分かれることです。臨床3期。

  • Crizotinib (PF-02341066)

    Crizotinib (PF-02341066)は一種の有効なc-MetとALK阻害剤で、細胞試験でIC50値が11 nMと24 nMです。

  • Foretinib (GSK1363089)

    Foretinib (GSK1363089)は一種のATP競争性的なHGFRとVEGFRの阻害剤です。Foretinib (GSK1363089)はMetとKDRに作用する効果が一番強くて、無細胞試験でこのIC50が0.4 nM と 0.9 nMに分かれますが、Ron、Flt-1/3/4、Kit、PDGFRα/βとTie-2に作用する効果が少し弱くて、FGFR1とEGFRに抑制活性を殆ど表しません。臨床2期。

  • Capmatinib (INCB28060)

    Capmatinib (INCB28060)は一種の新たで、ATP競争性的なc-MET阻害剤で、無細胞実験でIC50値が0.13 nMです。Capmatinib (INCB28060)はRONβ、EGFRとHER-3に活性を表しません。臨床1期。

    Features:Inactive against RONβ, another member of the c-MET RTK family, as well as EGFR and HER-3 (members of the EGFR RTK family).

  • Tivantinib (ARQ 197)

    Tivantinib (ARQ 197)は初めの非ATP競争性的なc-Met阻害剤で、無細胞実験でKi値が0.355 μMです。Tivantinib (ARQ 197)はRonに作用する活性が殆どなくて、EGFR、InsR、PDGFRαとFGFR1/4を抑制する作用がありません。臨床3期。

    Features:The first selective c-Met inhibitor to be advanced into human clinical trials.

  • PHA-665752

    PHA-665752は一種の有効で、選択性的で、ATP競争性的なc-Met阻害剤で、無細胞実験でIC50値が9 nMです。PHA-665752はc-Metに作用する選択性はRTKsとSTKsに作用する選択性より50倍以上が高くなります。

最近チェックしたアイテム

Tags: BMS-777607を買う | BMS-777607供給者 | BMS-777607を購入する | BMS-777607費用 | BMS-777607生産者 | オーダーBMS-777607 | BMS-777607代理店
×
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
お問い合わせ