|N-(4-((2-氨基-3-氯吡啶-4-基)氧基)-3-氟苯基)-4-乙氧基-1-(4-氟苯基)-2-氧代-1,2-二氢吡啶-3-甲酰胺|CsnPharm

CAS No.: 1025720-94-8

BMS 777607 Catalog No. CSN13471

Synonyms: BMS 817378;ASLAN-002

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, being 40-fold 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.

规格	价格	促销价格	库存	数量

400-920-2911

sales@csnpharm.cn

tech@csnpharm.cn

加入购物车大规格询价

加入收藏

产品咨询

400-920-2911

sales@csnpharm.cn

tech@csnpharm.cn

纯度 & 质量文件批次:

靶点选择性

生物活性

实验方案

技术信息

生物活性

靶点 Axl

IC50:1.1nM c-Met

IC50:3.9nM Ron

IC50:1.8nM Tyro3

IC50:4.3nM
描述The overexpression and activation of the Met receptor and its ligand HGF (hepatocyte growth factor) are associated with a wide variety of human malignancies, as well as the tumor invasion. BMS-777607 is a multiple Met kinase inhibitor with IC₅₀ values of 1.1 nM, 1.8 nM, 3.9 nM and 4.3 nM for Axl, Ron, Met and Tyro3, respectively, modestly potent to Mer, Flt-3 and Aurora B with IC₅₀ values of 14 nM, 16 nM and 78 nM, as well as inhibited Lck, VEGFR-2, TrkB, TrkA and PKA with IC₅₀>100 nM. BMS-777607 showed anti-proliferative effect on Met-driven H1993 with IC₅₀ value of 150 nM and U87 (glioblastoma, autocrine loop) with IC₅₀ value of 160 nM, but lacking activity against the Met-independent N87 cell line. Exposure to BMS-777607 for 30 min at concentration>33 nM caused reduction of p-Met in a dose-dependent manner in GTL-16 cells. Consistent with the cell growth inhibition assays, an in vivo study showed that once daily oral administration of BMS-777607 at dose of 6.25 mg/kg, 12.5 mg/kg, 25 mg/kg and 50 mg/kg for 14 consecutive days caused tumor growth inhibition in a GTL-16 xenograft model^[1].
作用机制BMS-777607 is an ATP-competitive inhibitor of the Met kinase.^[1]
细胞研究

Cell Data

Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
CHRF	10 μM	Function assay	-	inhibits cell division	25304900
DU145	0.1 μM	Function assay	-	exhibits inhibitory effect on HGF-induced cell scattering	20515943
DU145	0.01 μM	Function assay	-	suppresses HGF-induced cell migration	20515943

动物研究

剂量

Mice: 10 mg/kg - 25 mg/kg^[1] (p.o.); nude Mice: 50 mg/kg^[2] (p.o.)

给药途径

p.o.

动物药代数据

Animal	Mice^[3]	Rats^[3]	Dogs^[3]
Dose	10 mg/kg (p.o.) 5 mg/kg (i.v.)	10 mg/kg (p.o.) 5 mg/kg (i.v.)	5 mg/kg (p.o.) 1 mg/kg (i.v.)
Administration	p.o. i.v.	p.o. i.v.	p.o. i.v.
AUC_0→24h	90 μM·h (p.o.)	37.7 ± 19.2 μM·h (p.o.)	198 ± 68 μM·h (p.o.)
F		100% (p.o.)	100% (p.o.)
T_1/2	4.5 h (i.v.)	4.8 ± 1.5 h (i.v.)	4.9 h (i.v.)
T_max	0.5 h (p.o.)	1.7 ± 0.6 h (p.o.)	2.3 ± 1.5 h (p.o.)
CL	4.4 ml/min/kg (i.v.)	12.1 ± 1.4 ml/min/kg (i.v.)	0.82 ml/min/kg (i.v.)
C_max	17.6 μM (p.o.)	8.7 ± 4.2 μM (p.o.)	29.0 ± 6.9 μM (p.o.)
Vss	1.2 L/kg (i.v.)	1.0 ± 0.1 L/kg (i.v.)	0.22 L/kg (i.v.)

临床研究

NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
NCT01721148	Malignant Solid Tumour	Phase 1	Completed	-	-
NCT00605618	Advanced Solid Tumors	Phase 1 Phase 2	Completed	-	Australia, New South Wales ... more >> Local Institution Camperdown, New South Wales, Australia, 2050 Local Institution Kogarah, New South Wales, Australia, 2217 Collapse <<

参考文献

[1] Dai Y, Bae K, et al. Impact of the small molecule Met inhibitor BMS-777607 on the metastatic process in a rodent tumor model with constitutive c-Met activation. Clin Exp Metastasis. 2012 Mar;29(3):253-61.
[2] Wu CC, Weng CS, et al. Antitumor effects of BMS-777607 on ovarian cancer cells with constitutively activated c-MET. Taiwan J Obstet Gynecol. 2019 Jan;58(1):145-152.
[3] Schroeder GM, An Y, et al. Discovery of N-(4-(2-amino-3-chloropyridin-4-yloxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (BMS-777607), a selective and orally efficacious inhibitor of the Met kinase superfamily. J Med Chem. 2009 Mar 12;52(5):1251-4.

实验方案

计算器摩尔计算器总药量计算器工作液计算器
储存液制备
- 1 mg
- 5 mg
- 10 mg
- 1 mM
- 1.9497 mL
- 9.7487 mL
- 19.4974 mL
- 5 mM
- 0.3899 mL
- 1.9497 mL
- 3.8995 mL
- 10 mM
- 0.1950 mL
- 0.9749 mL
- 1.9497 mL

技术信息

CAS号

1025720-94-8

储存条件

粉末: Keep in dark place,Sealed in dry,2-8°C

液体: -20°C:3-6 月 -80°C:12月

分子式

C25H19ClF2N4O4

运输

蓝冰

分子量

512.89

别名

BMS 817378;ASLAN-002

溶解度

DMSO	110.0 mg/mL (214.5 mM)
Water	insoluble

动物实验配方

4% DMSO+45% PEG 300+5% Tween 80+water

5 mg/mL

大规格询价

号为必填项

姓名: 邮箱: 手机号:

留言:

提交

Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources

CHRF	10 μM	Function assay	-	inhibits cell division	25304900
DU145	0.1 μM	Function assay	-	exhibits inhibitory effect on HGF-induced cell scattering	20515943
DU145	0.01 μM	Function assay	-	suppresses HGF-induced cell migration	20515943
DU145	0.1 μM	Function assay	-	impairs HGF-mediated cell invasion	20515943
GTL-16	-	Kinase assay	-	inhibits Met kinase with IC50 of 100 nM	19260711
H1993	~10 μM	Growth inhibitory assay	-	IC50=150 nM	19260711
HPDE	10 μM	Function assay	-	blocks constitutive activation and decreased AKT signaling	26477314
KHT	-	Kinase assay	-	blocks the c-Met signaling pathway with IC50 of 10 nM	22286523
KHT	~1 μM	Function assay	-	prevents spontaneous KHT cell scattering with IC50 of 0.1-0.5 μM	22286523
KHT	~0.5 μM	Function assay	-	inhibits cell migration	22286523
KHT	~0.5 μM	Function assay	-	inhibits cell invasion	22286523
KHT	~10 μM	Growth inhibitory assay	-	inhibits KHT cell proliferation	22286523
PC-3	0.1 μM	Function assay	-	exhibits inhibitory effect on HGF-induced cell scattering	20515943
PC-3	0.01 μM	Function assay	-	suppresses HGF-induced cell migration	20515943
PC-3	0.1 μM	Function assay	-	impairs HGF-mediated cell invasion	20515943
PC-3	~10 μM	Growth inhibitory assay	-	reduces cell proliferation	20515943
SF126	~3 μM	Kinase assay	-	blocks AXL phosphorylation	26848524
SF126	12.5 μM	Cytoxicity assay	-	decreases glioma cell viability	26848524
SF126	12.5 μM	Apoptosis assay	-	induces glioma cell apoptosis	26848524
SF126	12.5 μM	Function assay	-	blocks glioma cell migration and invasive growth pattern	26848524
T-47D	~5 μM	Growth inhibitory assay	-	inhibits cell proliferation	23468529
T-47D	10 μM	Function assay	-	Induces polyploidy by 86 %	23468529
T-47D	10 μM	Function assay	-	inhibits AURK-B function and induces its protein degradation	23468529
U118MG	~3 μM	Kinase assay	-	blocks AXL phosphorylation	26848524
U118MG	12.5 μM	Cytoxicity assay	-	decreases glioma cell viability	26848524
U118MG	12.5 μM	Apoptosis assay	-	induces glioma cell apoptosis	26848524
U118MG	12.5 μM	Function assay	-	blocks glioma cell migration and invasive growth pattern	26848524
U87	~10 μM	Growth inhibitory assay	-	IC50=160 nM	19260711
ZR-75-1	~5 μM	Growth inhibitory assay	-	inhibits cell proliferation	23468529
ZR-75-1	10 μM	Function assay	-	Induces polyploidy by 88%	23468529

靶点	Description	IC50
Axl		IC50:1.1nM
c-Met		IC50:3.9nM
Ron		IC50:1.8nM
Tyro3		IC50:4.3nM

BMS 777607 Catalog No. CSN13471

靶点选择性

请登录您的专属账户

确认信息