A MELK inhibitor
MELK-8a is an inhibitor of maternal embryonic leucine zipper kinase (MELK; IC50 = 0.002 ?M).1 It is selective for MELK over FLT3, haspin, KIT, and PDGFRα, (IC50s = 0.18, 0.19, >10, and 0.42 ?M, respectively), as well as a panel of 456 kinases at 1 ?M. MELK-8a inhibits the proliferation of MDA-MB-468 and MCF-7 breast cancer cells (IC50s = 0.11 and 3.68 ?M).
1.Touré, B.B., Giraldes, J., Smith, T., et al.Toward the validation of maternal embryonic leucine zipper kinase: Discovery, optimization of highly potent and selective inhibitors, and preliminary biology insightJ. Med. Chem.59(10)4711-4723(2016)
Cell experiment: | MDA-MB-468 and MCF7 cells are seeded in growth medium into 96-well plates at 1000 and 4000 cells/well, respectively. Sixteen hours after plating, MELK-8a are added and incubated for 7 days. For each well, ATPLite reagent is added and incubated. Luminescence is measured on an multilabel plate reader[1]. |
Animal experiment: | Mice: For pharmacokinetic studies, the intravenous and oral dose is prepared in a solution containing 5% ethanol, 100% PG, 5% CremophorEL, and 80% PBS. The subcutaneous dose is formulated in 10% PG and 25% (20%, v/v) Solutol. Plasma samples are collected at specified time points and stored frozen (?20 °C) until MELK-8a analysis. An LC?MS/MS method is used to quantitate MELK-8a drug levels in plasma[1]. |
参考文献: [1]. Touré BB, et al. Toward the Validation of Maternal Embryonic Leucine Zipper Kinase: Discovery, Optimization of Highly Potent and Selective Inhibitors, and Preliminary Biology Insight. J Med Chem. 2016 May 26;59(10):4711-23. | |
动态评分
0.0