产品说明书
GSK461364
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同义名 : | GSK461364A |
| CAS号 : | 929095-18-1 | |
| 货号 : | A313486 | |
| 分子式 : | C27H28F3N5O2S | |
| 纯度 : | 99%+ | |
| 分子量 : | 543.604 | |
| MDL号 : | MFCD12755419 | |
| 存储条件： |
粉末 Sealed in dry,2-8°C 液体 -20°C:3-6个月-80°C:12个月 |
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| 溶解度 : |
DMSO: 50 mg/mL(91.98 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO |
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| 动物实验配方： |
IP 2% DMSO+2% Tween80+30% PEG300+water 1 mg/mL clear PO 0.5% CMC-Na 21 mg/mL suspension |
| 生物活性 | |||
|---|---|---|---|
| 靶点 |
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| 描述 | Polo-like kinase 1 (Plk1) is a conserved serine/threonine kinase that plays an essential role in regulating the many processes involved in mitotic entry and progression. In humans, Plk1 is expressed primarily during late G2 and M phases and, in conjunction with Cdk1/cyclin B1, acts as master regulatory kinases for the myriad protein substrates involved in mitosis. Plk1 overexpression is strongly associated with cancer and has been correlated with poor prognosis in a broad range of human tumor types. GSK461364 is a potent, selective, reversible, ATP-competitive Plk1 inhibitor with a Ki value of 2.2 nM. To further explore selectivity, GSK461364 was tested against an in-house panel of 48 kinases. GSK461364 had at least 1,000-fold selectivity for Plk1 over the majority of kinases tested. In a NSCLC line A549, treatment with GSK461364 above 10 nmol/L for 20 hours caused increased 4N DNA content indicating G2-M arrest. With extended exposure duration, increased sub-2N DNA indicating increased cell death was observed for GSK461364 concentrations of >10 nmol/L. In A549 cells, at 20 nmol/L GSK461364 for 16 hours, a significant increase in mitotic cells was evident. In a proliferation assay, 89% of cell lines (66 of 74 lines) responded to GSK461364 with a gI50 (concentration required to inhibit 50% cell growth) of ≤100 nmol/L. GSK461364 was dosed i.p. in mice bearing Colo205 (colorectal) xenograft tumors, higher intermittent dosing with a q4dx3 (one dose every 4 days repeated thrice) schedule at 100 mg/kg resulted in 18 days TGD (tumor growth delay) and one PR (partial regression) out of five mice treated. More frequent lower dosing with 50 mg/kg q2dx6 schedule resulted in longer TGD (39 days) and 2PR. Extending the schedule of 50 mg/kg q2dx12 resulted in longer TGD (62 days) with one CR and 3PR observed, efficacy approaching the antitumor activity of the positive control agent paclitaxel[2]. | ||
| 细胞研究 | |||||
|---|---|---|---|---|---|
| 细胞系 | 浓度 | 检测类型 | 检测时间 | 活动说明 | 数据源 |
| human MV4-11 cells | Cytotoxicity assay | 24 h | Cytotoxicity against human MV4-11 cells after 24 hrs by CellTiter-Blue assay, GI50=0.679 μM | 26191363 | |
| 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 |
| NCT00536835 | Lymphoma, Non-Hodgkin | Phase 1 | Completed | - | United Kingdom ... 展开 >> GSK Investigational Site Sutton, Surrey, United Kingdom, SM2 5PT GSK Investigational Site Belfast, Northern Ireland, United Kingdom, BT9 7AB GSK Investigational Site London, United Kingdom, W12 0NN 收起 << |
| 实验方案 | |||
|---|---|---|---|
| 1mg | 5mg | 10mg | |
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1 mM 5 mM 10 mM |
1.84mL 0.37mL 0.18mL |
9.20mL 1.84mL 0.92mL |
18.40mL 3.68mL 1.84mL |
