产品描述: VS-5584 is a pan-PI3K/mTOR kinase inhibitor with IC50s of 16 nM, 68 nM, 42 nM, 25 nM, and 37 nM for PI3Kα, PI3Kβ, PI3Kδ, PI3Kγ and mTOR, respectively. VS-5584 simultaneously blocks mTORC2 as well as mTORC1. |
靶点:
PI3Kα:16 nM (IC50);PI3Kγ:25 nM (IC50);PI3Kδ:42 nM (IC50);PI3Kβ:68 nM (IC50);Vps34:7470 nM (IC50);mTOR:37 nM (IC50);mTORC1;mTORC2;DNA-PK:1270 nM (IC50);PI3K;mTOR |
体内研究:
Nude mice bearing MDA-MB-231 human breast cancer tumors are treated for 5 days with once daily oral VS-5584 (25 mg/kg). Oral treatment of tumor bearing mice with VS-5584 reduces cancer atem cells analyzed from extracted tumors. Mice are implanted with tumor fragments from a docetaxel-resistant patient-derived triple negative breast cancer. Mice are treated with VS-5584 (20 mg/kg, po, qd) or Docetaxel (20 mg/kg, i.v.). Oral VS-5584 induces tumor regression in a Docetaxel-resistant patient-derived breast cancer model. A single oral dose of VS-5584 is rapidly absorbed with a tmax of 0.9 hours and an elimination half-life of 10 hours. To determine the pharmacokinetic and pharmacodynamic relationship in tumors, PC3-tumor–bearing mice are treated with a single dose of VS-5584 and plasma and tumors are harvested after 6 hours and analyzed for concentrations of VS-5584 and effects on target efficacy biomarkers. Plasma levels of VS-5584 increase dose-dependently. For evaluation of efficacy in a Rapamycin-sensitive PC3 engraftment model, tumor-bearing mice are treated with VS-5584 for 28 days in comparison with the rapalog Everolimus. VS-5584 is well tolerated at both doses tested (11 and 25 mg/kg) with minimal weight loss (mean 4.7% on day 27). Treatment with VS-5584 leads to significant tumor growth inhibition (TGI) of 79% and 113% for 11 and 25 mg/kg, respectively |
参考文献:
1. Hart S, et al. VS-5584, a novel and highly selective PI3K/mTOR kinase inhibitor for the treatment of cancer. Mol Cancer Ther, 2013, 12(2), 151-161. |
溶解性:
DMSO : 33.33 mg/mL (94.04 mM; Need ultrasonic) |
保存条件:
-20℃ |
配置溶液浓度参考:
|
1mg |
5mg |
10mg |
1 mM |
2.822 ml |
14.108 ml |
28.216 ml |
5 mM |
0.564 ml |
2.822 ml |
5.643 ml |
10 mM |
0.282 ml |
1.411 ml |
2.822 ml |
50 mM |
0.056 ml |
0.282 ml |
0.564 ml |
|
注意: |
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