产品名称

英文名称：GSK461364

同义词

929095-18-1、GSK461364、GSK-461364、GSK 461364、GSK-461364A、(R)-5-(6-((4-methylpiperazin-1-yl)methyl)-1H-benzo[d]imidazol-1-yl)-3-(1-(2-(trifluoromethyl)phenyl)ethoxy)thiophene-2-carboxamide、GSK461364A、UNII-8QO27TK6Q4、8QO27TK6Q4、5-[6-[(4-Methyl-1-piperazinyl)

产品性质

CAS编号：929095-18-1

分子式：C27H28F3N5O2S

分子量：543.62

PubChem编号：15983966

英文别名：929095-18-1|GSK461364|GSK-461364|GSK 461364|GSK-461364A|(R)-5-(6-((4-methylpiperazin-1-yl)methyl)-1H-benzo[d]imidazol-1-yl)-3-(1-(2-(trifluoromethyl)phenyl)ethoxy)thiophene-2-carboxamide|GSK461364A|UNII-8QO27TK6Q4|8QO27TK6Q4|5-[6-[(4-Methyl-1-piperazinyl)

规格或纯度：98%

英文名称：GSK461364

生化机理：GSK-461364A is a potent small molecule Polo-like kinase 1 (PLK1) inhibitor with a Ki of 2.2 nM. GSK-461364A is an ATP-competitive inhibitor of Plk1 and forms a rapidly reversible complex with Plk1.GSK461364 is an imidazotriazine derivate that inhibits polo-like kinase 1 (Plk1) in a potent, reversible, ATP-competitive, and highly selective manner (Kiapp <0.5 nM vs. 0.86 μM for Plk2 and 200 μM for Plk3; ATP Kmapp = 16 μM), exhibiting much reduced or little potency toward a panel of 262 kinases. GSK461364A inhibits the growth of various cancer cultures (IG50 <100 nM) as a result of either growth arrest (cytostasis) or cytotoxicity in vitro and effectively suppresses the expansion of various human tumor exnografts in mice in vivo (25 or 50 mg/kg i.p. q2dx12).

储存温度：-20°C储存,充氩

运输条件：超低温冰袋运输

产品介绍：产品介绍GSK461364是高效可逆的ATP竞争性PIK1抑制剂。Polo样激酶（PIK）属于丝氨酸苏氨酸激酶家族，是DNA损伤应答和细胞周期进程的重要调节剂。体外实验相比于Plk2和Plk3，GSK461364对Plk1至少有390倍选择性，相比于其它48种激酶具有1000倍选择性。GSK461364对多种肿瘤细胞系（超过120种）具有抗增殖活性，并能高效地抑制这些细胞系中超过83%和91%的增殖。体内试验在多种异种移植物模型中腹腔注射GSK461364引起肿瘤消退或延迟肿瘤生长。GSK461364抑制体内Plk1，导致有丝分裂停滞，体现在包含单极或收缩的有丝分裂纺锤体的异常有丝分裂指标。临床试验二期临床最终推荐的GSK461364静脉注射剂量为225 mg。而且，进一步临床研究中，GSK461364与预防性抗凝药物共同给药。

ALogP：4.7

IUPAC Name：5-[6-[(4-methylpiperazin-1-yl)methyl]benzimidazol-1-yl]-3-[(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide

INCHI：InChI=1S/C27H28F3N5O2S/c1-17(19-5-3-4-6-20(19)27(28,29)30)37-23-14-24(38-25(23)26(31)36)35-16-32-21-8-7-18(13-22(21)35)15-34-11-9-33(2)10-12-34/h3-8,13-14,16-17H,9-12,15H2,1-2H3,(H2,31,36)/t17-/m1/s1

InChi Key：ZHJGWYRLJUCMRT-QGZVFWFLSA-N

Canonical SMILES：CC(C1=CC=CC=C1C(F)(F)F)OC2=C(SC(=C2)N3C=NC4=C3C=C(C=C4)CN5CCN(CC5)C)C(=O)N

Isomeric SMILES：C[C@H](C1=CC=CC=C1C(F)(F)F)OC2=C(SC(=C2)N3C=NC4=C3C=C(C=C4)CN5CCN(CC5)C)C(=O)N

PubChem CID：15983966

CAS Registry No.：929095-18-1

DiscoveRx TREEspot：GSK-461364A|

ChEMBL Ligand：CHEMBL1908394

溶解性：DMSO 10 mg/mL Water <1 mg/mL Ethanol 30 mg/mL

敏感性：对湿度敏感

产品包装