BMS-777607

別名：BMS 817378

製品コード：S1561 純度：99.64%

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.

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
5mg	JPY 22000	国内在庫あり
50mg	JPY 100500	国内在庫あり
1g	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] よく尋ねられる質問

文献中Selleckの製品使用例（56）

製品安全説明書

現在のバッチを見る：純度： 99.64%

99.64

BMS-777607関連製品

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関連化合物ライブラリー	Kinase Inhibitor Library Tyrosine Kinase Inhibitor Library PI3K/Akt Inhibitor Library Cell Cycle compound library Angiogenesis Related compound Library	もっと見る

シグナル伝達経路

c-Met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

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)	もっとクリックする
1.1 nM	1.8 nM	3.9 nM	4.3 nM	14 nM	もっとクリックする

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
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
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-05-22)
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

参考
[1] Schroeder GM, et al. J Med Chem, 2009, 52(5), 1251-1254. [2] Dai Y, et al. Mol Cancer Ther, 2010, 9(6), 1554-1561. [3] Dai Y, et al. Clin Exp Metastasis, 2012, 29, 253-261. [4] Kim KS, et al. J Med Chem, 2008, 51(17), 5330-5341. + 展開

参考

[4] Kim KS, et al. J Med Chem, 2008, 51(17), 5330-5341.

+ 展開

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	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1个月-20°Cin solvent

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
=	×	×

希釈計算器分子量計算器

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）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

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。

技術サポート

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Handling Instructions

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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.

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):