2096992-20-8
基本信息
NVP-MELK8a hydrochloride
物理化學(xué)性質(zhì)
報(bào)價(jià)日期 | 產(chǎn)品編號 | 產(chǎn)品名稱 | CAS號 | 包裝 | 價(jià)格 |
2024/11/08 | HY-100368A | MELK8A HYDROCHLORIDE MELK-8a hydrochloride | 2096992-20-8 | 1mg | 1500元 |
2024/11/08 | HY-100368A | MELK8A HYDROCHLORIDE MELK-8a hydrochloride | 2096992-20-8 | 5mg | 2800元 |
2024/11/08 | HY-100368A | MELK8A HYDROCHLORIDE MELK-8a hydrochloride | 2096992-20-8 | 10mM * 1mLin DMSO | 2889元 |
常見問題列表
IC50: 2 nM (MELK)
MELK-8a remains very potent (IC 50 =140 nM) when the ATP concentration in the biochemical assay is shifted from 20 μM to 2 mM. Its potency is well tracked between full-length MELK versus catalytic domain construct (5 nM versus 2 nM). It only inhibits seven off-target kinases in addition to MELK with >85% inhibition of binding at 1 μM demonstrating great selectivity. The compound is at least 90-fold more selective in targeting MELK in all cases. MELK-8a is fairly soluble (0.22 g/L at pH 6.8) and shows a good permeability in the Caco-2 assay. MELK-8a inhibits the growth of MDA-MB-468 cells and MCF-7 cells with an IC 50 of approximately 0.06 and 1.2 μM, respectively.
Subcutaneous administration of MELK-8a at 30 mg/kg in C57BL/6 mice results in good plasma exposure. The compound adsorption into the systemic circulation is rapid (T max =0.4 h) and peak plasma concentration reaches 6.6 μM. An ascending dose PK study in female athymic nude mice shows that the rate of compound release is maximal at 120 mg/kg and all clearance mechanisms can be saturated at 240 mg/kg. However, when administered orally at 10 mg/kg in C57BL/6 male mice, it shows very poor PK (3.6% oral bioavailability) consistent with very high in vivo clearance.