产品名称

英文名称：LY2801653

同义词

Merestinib、1206799-15-6、LY2801653、LY-2801653、N-(3-fluoro-4-((1-methyl-6-(1H-pyrazol-4-yl)-1H-indazol-5-yl)oxy)phenyl)-1-(4-fluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxamide、Merestinib [USAN]、N-[3-fluoro-4-[1-methyl-6-(1H-pyrazol-4-yl)indazol-

产品性质

CAS编号：1206799-15-6

分子式：C30H22F2N6O3

分子量：552.53

PubChem编号：44603533

英文别名：Merestinib|1206799-15-6|LY2801653|LY-2801653|N-(3-fluoro-4-((1-methyl-6-(1H-pyrazol-4-yl)-1H-indazol-5-yl)oxy)phenyl)-1-(4-fluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxamide|Merestinib [USAN]|N-[3-fluoro-4-[1-methyl-6-(1H-pyrazol-4-yl)indazol-

规格或纯度：98%

英文名称：LY2801653

生化机理：Description IC50 Value 2 nM(Ki value) LY2801653 is a potent, orally bioavailable, small-molecule inhibitorLY2801653 targeting MET kinase. in vitro LY2801653 is a type-II ATP competitive, slow-off inhibitor of MET tyrosine kinase with a dissociation constant (K(i)) of 2 nM, a pharmacodynamic residence time (K(off)) of 0.00132 min(-1) and t(1/2) of 525 min [1]. LY2801653 was found to have potent activity against several other receptor tyrosine oncokinases including MST1R, FLT3, AXL, MERTK, TEK, ROS1, DDR1/2 and against the serine/threonine kinases MKNK1/2. in vivo LY2801653 demonstrated in vitro effects on MET pathway-dependent cell scattering and cell proliferation; in vivo anti-tumor effects in MET amplified (MKN45), MET autocrine (U-87MG, and KP4) and MET over-expressed (H441) xenograft models; and in vivo vessel normalization effects . Clinical trial LY2801653 is currently in phase 1 clinical testing in patients with advanced cancer (trial I3O-MC-JSBA, NCT01285037).

储存温度：-20°C储存

运输条件：超低温冰袋运输

产品介绍：产品介绍LY2801653是一种有效的c-MET激酶抑制剂，IC50值为2 nM。c-Met激酶也被称为肝细胞生长因子受体（HGFR），是一种膜相关的酪氨酸激酶受体。HGF是该受体的唯一配体。HGF的结合诱导c-MET的构象变化，激活酪氨酸激酶活性，进而激活下游信号。c-MET信号调节各种细胞功能，包括细胞增殖、存活、凋亡，c-Met激酶的异常激活可能引发肿瘤生长、血管生成和癌转移。生化和结晶研究表明，LY2801653是一种强效的ATP竞争性c-MET激酶抑制剂，通过抑制c-MET激酶的磷酸化而起作用。体外研究表明，0.01到10 μM的LY2801653能够完全阻止HGF诱导的由c-MET激酶调节的DU-145细胞散射，这表明c-MET激酶的活性被抑制。使用一系列细胞系筛选LY2801653，发现与那些不表达MET基因的细胞相比，在MET基因表达的的细胞系中，LY2801653具有更有效的抗增殖活性。在U-87MG异种移植的小鼠中，分别用低剂量（1.3 mg/kg）和高剂量（12 mg/kg）LY2801653 ，每天一次，治疗28天，并且将组织表征。研究发现，低剂量的治疗导致c-MET激酶相关的凋亡区域减少，而高剂量治疗导致凋亡区域显著降低。此外，高剂量的LY2801653抑制c-MET激酶相关的血管生成，血管趋于正常[2]。这些结果表明LY2801653能够通过抑制c-MET激酶活性，干扰c-MET激酶的下游信号通路。

ALogP：4.7

IUPAC Name：N-[3-fluoro-4-[1-methyl-6-(1H-pyrazol-4-yl)indazol-5-yl]oxyphenyl]-1-(4-fluorophenyl)-6-methyl-2-oxopyridine-3-carboxamide

INCHI：InChI=1S/C30H22F2N6O3/c1-17-3-9-23(30(40)38(17)22-7-4-20(31)5-8-22)29(39)36-21-6-10-27(25(32)12-21)41-28-11-18-16-35-37(2)26(18)13-24(28)19-14-33-34-15-19/h3-16H,1-2H3,(H,33,34)(H,36,39)

InChi Key：QHADVLVFMKEIIP-UHFFFAOYSA-N

Canonical SMILES：CC1=CC=C(C(=O)N1C2=CC=C(C=C2)F)C(=O)NC3=CC(=C(C=C3)OC4=C(C=C5C(=C4)C=NN5C)C6=CNN=C6)F

Isomeric SMILES：CC1=CC=C(C(=O)N1C2=CC=C(C=C2)F)C(=O)NC3=CC(=C(C=C3)OC4=C(C=C5C(=C4)C=NN5C)C6=CNN=C6)F

PubChem CID：44603533

ChEMBL Ligand：CHEMBL3545307

BindingDB Ligand：50172078

RCSB PDB Ligand：L1X

CAS Registry No.：1206799-15-6

溶解性：≥27.65 mg/mL in DMSO; insoluble in H2O; ≥5.02 mg/mL in EtOH with gentle warming and ultrasonic

象形图：

信号词：Danger

危险声明：H351 Suspected of causing cancerH302 Harmful if swallowedH372 Causes damage to organs through prolonged or repeated exposureH360 May damage fertility or the unborn child

预防措施声明：P280,P405,P501,P264,P260,P270,P330,P203,P301+P317,P318,P319

产品包装