BMS-777607

別名:BMS 817378

BMS-777607 (BMS 817378) 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.

BMS-777607化学構造

CAS No. 1025720-94-8

サイズ 価格(税別) 在庫状況
10mM (1mL in DMSO) JPY 37500 国内在庫あり
JPY 22000 国内在庫あり
JPY 100500 国内在庫あり
JPY 295500 国内在庫なし(納期7~10日)

代表番号: 045-509-1970|電子メール:[email protected]
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文献中Selleckの製品使用例(56)

製品安全説明書

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BMS-777607関連製品

シグナル伝達経路

c-Met阻害剤の選択性比較

Cell Data

Cell Lines Assay Type Concentration Incubation Time 活性情報 PMID
T-47D Function assay 10 μM Induces polyploidy by 86 % 23468529
ZR-75-1 Growth inhibitory assay ~5 μM inhibits cell proliferation 23468529
T-47D Growth inhibitory assay ~5 μM inhibits cell proliferation 23468529
KHT Growth inhibitory assay ~10 μM inhibits KHT cell proliferation 22286523
KHT Function assay ~0.5 μM inhibits cell invasion 22286523
KHT Function assay ~0.5 μM inhibits cell migration 22286523
KHT Function assay ~1 μM prevents spontaneous KHT cell scattering with IC50 of 0.1-0.5 μM 22286523
PC-3 Growth inhibitory assay ~10 μM reduces cell proliferation 20515943
DU145 Function assay 0.1 μM impairs HGF-mediated cell invasion 20515943
PC-3 Function assay 0.1 μM impairs HGF-mediated cell invasion 20515943
DU145 Function assay 0.01 μM suppresses HGF-induced cell migration 20515943
PC-3 Function assay 0.01 μM suppresses HGF-induced cell migration 20515943
DU145 Function assay 0.1 μM exhibits inhibitory effect on HGF-induced cell scattering 20515943
PC-3 Function assay 0.1 μM exhibits inhibitory effect on HGF-induced cell scattering 20515943
ZR-75-1 Function assay 10 μM Induces polyploidy by 88% 23468529
T-47D Function assay 10 μM inhibits AURK-B function and induces its protein degradation 23468529
CHRF Function assay 10 μM inhibits cell division 25304900
HPDE Function assay 10 μM blocks constitutive activation and decreased AKT signaling 26477314
U118MG Kinase assay ~3 μM blocks AXL phosphorylation 26848524
SF126 Kinase assay ~3 μM blocks AXL phosphorylation 26848524
U118MG Cytoxicity assay 12.5 μM decreases glioma cell viability 26848524
SF126 Cytoxicity assay 12.5 μM decreases glioma cell viability 26848524
U118MG Apoptosis assay 12.5 μM induces glioma cell apoptosis 26848524
SF126 Apoptosis assay 12.5 μM induces glioma cell apoptosis 26848524
U118MG Function assay 12.5 μM blocks glioma cell migration and invasive growth pattern 26848524
SF126 Function assay 12.5 μM blocks glioma cell migration and invasive growth pattern 26848524
GTL16 Function assay 6.25 mg/kg Cmax in human GTL16 cells xenografted athymic mouse at 6.25 mg/kg, po, Cmax = 4.5 μM. 19260711
GTL16 Function assay 50 mg/kg Cmax in human GTL16 cells xenografted athymic mouse at 50 mg/kg, po, Cmax = 43.7 μM. 19260711
GTL16 Function assay 30 mins Inhibition of Met phosphorylation in human GTL16 cells after 30 mins, IC50 = 0.02 μM. 19260711
GTL16 Antiproliferative assay 72 hrs Antiproliferative activity against Met-dependent human GTL16 cells after 72 hrs by MTS assay, IC50 = 0.1 μM. 19260711
NCI-H1993 Antiproliferative assay 72 hrs Antiproliferative activity against Met-dependent human NCI-H1993 cells after 72 hrs by MTS assay, IC50 = 0.15 μM. 19260711
U87 Antiproliferative assay 72 hrs Antiproliferative activity against Met-driven human U87 cells after 72 hrs by MTS assay, IC50 = 0.16 μM. 19260711
BAF3 Cytotoxicity assay 72 hrs Cytotoxicity against mouse BAF3 cells expressing TPR-Met assessed as growth inhibition after 72 hrs, IC50 = 0.1884 μM. 24792774
DU145 Antiinvasive assay 1 hr Antiinvasive activity in human DU145 cells assessed as inhibition of HGF-induced cell motility preincubated for 1 hr before HGF treatment measured after 24 hrs by cell scattering assay, IC50 = 0.2 μM. 24900830
MKN45 Cytotoxicity assay 72 hrs Cytotoxicity against human MKN45 cells assessed as growth inhibition after 72 hrs, IC50 = 0.2858 μM. 24792774
NCI-H1993 Cytotoxicity assay 48 hrs Cytotoxicity against human NCI-H1993 cells after 48 hrs by MTT assay, IC50 = 1.108 μM. 24900830
MGHU3 Antiproliferative assay 72 hrs Antiproliferative activity against human MGHU3 cells after 72 hrs by CellTiter-Glo assay 30309671
RT112 Antiproliferative assay 72 hrs Antiproliferative activity against human RT112 cells after 72 hrs by CellTiter-Glo assay 30309671
KHT Kinase assay blocks the c-Met signaling pathway with IC50 of 10 nM 22286523
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
Saos-2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells 29435139
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells) 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells 29435139
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SJ-GBM2 cells 29435139
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells 29435139
MG 63 (6-TG R) qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for MG 63 (6-TG R) cells 29435139
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生物活性

製品説明 BMS-777607 (BMS 817378) 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.
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.
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)
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1.1 nM 1.8 nM 3.9 nM 4.3 nM 14 nM
In Vitro
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]

Kinase Assay 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 DMSO and evaluated at 10 concentrations, in duplicate.
細胞実験 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.

実験結果図 Methods Biomarkers 結果図 PMID
Western blot p-c-Met / c-Met / p-FAK / p-c-Src / p-Akt / p-S6K / p-S6 p53 / p21 / Survivin / p-Rb / Rb 22639908
Immunofluorescence α-tubulin / survivin 24444656
In Vivo
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]

動物実験 動物モデル Rodent fibrosarcoma KHT cells are established in female C3H/HeJ mice.
投与量 10-25 mg/kg.
投与経路 Oral gavage once daily.
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

化学情報

分子量 512.89 化学式

C25H19ClF2N4O4

CAS No. 1025720-94-8 SDF Download BMS-777607 SDFをダウンロードする
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
保管

In vitro
Batch:

DMSO : 100 mg/mL ( (194.97 mM); 吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Water : Insoluble

Ethanol : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量 濃度 体積 分子量

投与溶液組成計算機(クリア溶液)

ステップ1:実験データを入力してください。(実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します)

mg/kg g μL

ステップ2:投与溶媒の組成を入力してください。(ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください)

% DMSO % % Tween 80 % ddH2O
%DMSO %

計算結果:

投与溶媒濃度: mg/ml;

DMSOストック溶液調製方法: mg 試薬を μL DMSOに溶解する(濃度 mg/mL, 注:濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法:Take μL DMSOストック溶液に μL PEG300,を加え、完全溶解後μL Tween 80,を加えて完全溶解させた後 μL ddH2O,を加え完全に溶解させます。

投与溶媒調製方法:μL DMSOストック溶液に μL Corn oil,を加え、完全溶解。

注意:1.ストック溶液に沈殿、混濁などがないことをご確認ください;
2.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

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よくある質問(FAQ)

質問1:
What formulation can we use to dissolve S1561 for mice in vivo study?

回答
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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