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| 活性类型 | 活性值-log(M) | 作用机制 | 期刊 | 参考文献(PubMed IDs) |
|---|
GSK461364, 丝氨酸/苏氨酸蛋白激酶 PLK1 抑制剂
有货
为什么选择此级别
Moligand™ 级 ，适用于对基线干扰要求严格的色谱和分析工作流程。
储存与运输
-80℃储存。特低温运输 。请查阅批次 COA 获取详细规格。
质量文档
SDS、COA、产品数据表及规格说明书均可下载。可通过批号查询获取批次 COA。
文献证明
在色谱分析、有机合成和交叉偶联反应领域已被 0 篇同行评审文献引用。
概述
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。
Information
GSK461364 (GSK461364A) inhibits purifiedPlk1withKiof 2.2 nM in a cell-free assay. It is more than 1000-fold selective against Plk2/3. Phase 1.
In vitro
GSK461364 inhibits cancer cell line proliferation from multiple origins with minimal toxicity in nondividing human cells. RNA silencing of WT p53 increases the antiproliferative activity of GSK461364. As many cancer therapies tend to be more effective in p53 WT patients, the higher sensitivity of p53-deficient tumors toward GSK461364 could potentially offer an opportunity to treat tumors that are refractory to other chemotherapies as well as early line therapy for these genotypes. GSK461364 is a thiophene amide that inhibits purified Plk1 enzyme in vitro with a Ki of 2 nM and has >100-fold selectivity for Plk1 compared with Plk2 and Plk3. GSK461364 is a potent inhibitor of cell proliferation causing 50% growth inhibition (GI50) below 100 nM in most of the cell lines tested with limited toxicity against human nonproliferating cells. Inhibition of cell cycle progression is concentration dependent with initial delay at G2 phase at high GSK461364 concentrations and arrest at M phase at lower concentrations. Currently, GSK461364 is in a dose-escalation first-time-in-human trial. Cell lines with mutations in the TP53 gene tended to be more sensitive to GSK461364, and that inhibiting the p53 response by RNA silencing confers increased sensitivity in some p53 wild-type (WT) cells. Furthermore, these more sensitive cell lines also have increased levels of chromosome instability, a characteristic associated with TP53 mutations. In preclinical testing, GSK461364 shows antiproliferative activity against multiple (>120) tumor cell lines and potently inhibits the proliferation of greater than 83% and 91% of these cell lines, with IC50 values lower than 50 and 100 nM, respectively.
In vivo
Cell culture growth inhibition by GSK461364 can be cytostatic or cytotoxic but leads to tumor regression in xenograft tumor models under proper dose scheduling. GSK461364 shows clear antitumor activity in human tumor xenograft models. GSK461364 shows a dose-dependent mitotic arrest in mouse xenografts, which correlates with effects on tumor growth. Intraperitoneal administration of GSK461364 causes regression or tumor growth delay in different xenograft models, including Colo205 xenografts. Suppression of Plk1 in vivo by using GSK461364 results in mitotic arrest with aberrant mitotic figures consisting of monopolar or collapsed mitotic spindles.
Cell Data
cell lines：
Concentrations：10 nM
Incubation Time：72 hours
Powder Purity:≥96%
规格
英文别名
GSK461364A | 5-(6-((4-methylpiperazin-1-yl)methyl)-1H-benzo[d]imidazol-1-yl)-3-((R)-1-(2-(trifluoromethyl)phenyl)ethoxy)thiophene-2-carboxamide
规格或纯度
Moligand™, 10mM in DMSO
英文名称
GSK461364
生化机理
在无细胞试验中，GSK461364（GSK461364A）抑制纯化的 Plk1 的Ki值为 2.2 nM。它对 Plk2/3 的选择性超过 1000 倍。第 1 阶段
储存条件
-80℃储存
运输条件
特低温运输
作用类型
抑制剂
作用机制
丝氨酸/苏氨酸蛋白激酶 PLK1 抑制剂
名称和识别符
分子类型
小分子
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
分子量
543.62
Reaxy-Rn
15473760
Reaxys-RN link address
https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=15473760&ln=
技术文档
高级数据
产品属性
| ALogP | 4.7 |
|---|
关联靶点（人）
PLK1
Tchem
丝氨酸/苏氨酸蛋白激酶 PLK1(Serine/threonine-protein kinase PLK1)
(4 活性数据)
NUAK2
Tchem
NUAK 家族 SNF1 类激酶 2(NUAK family SNF1-like kinase 2)
(1 活性数据)
化学和物理性质
溶解性
Solubility (25°C) In vitro DMSO: 48 mg/mL (198.96 mM); Ethanol: 12 mg/mL (49.74 mM); Water: Insoluble;
质检证书（CoA,COO,BSE/TSE 和分析图谱)
C of A & Other Certificates(BSE/TSE, COO):
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通过匹配包装上的批号来查找并下载产品的 COA，每批产品都进行了严格的验证，您可放心使用！
| 批号(Lot Number) | 证书类型 | 货号 |
|---|---|---|
 L2220020 |
分析证书 | G408291 |
溶液计算器
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