• 產(chǎn)品描述：

  MELK-8a hydrochloride是一種新穎的母體胚胎亮氨酸拉鏈激酶（MELK）抑制劑，其IC50值為2 nM。

• 靶點(diǎn)： IC50: 2 nM (MELK);MELK

• 體外研究：
  MELK-8a remains very potent (IC50=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 IC50 of approximately 0.06 and 1.2 μM, respectively.

• 體內(nèi)研究：
  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 (Tmax=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.

• 參考文獻(xiàn)：
  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.

• 溶解性： soluble  in  DMSO

• 保存條件： -20℃

• 配置溶液濃度參考：
  

  	1mg	5mg	10mg
  1 mM	2.132 ml	10.661 ml	21.321 ml
  5 mM	0.426 ml	2.132 ml	4.264 ml
  10 mM	0.213 ml	1.066 ml	2.132 ml
  50 mM	0.043 ml	0.213 ml	0.426 ml

• 注意：部分產(chǎn)品我司僅能提供部分信息，我司不保證所提供信息的權(quán)威性，僅供客戶參考交流研究之用。

輸入產(chǎn)品批號：

本計(jì)算器可幫助您計(jì)算出特定溶液中溶質(zhì)的質(zhì)量、溶液濃度和體積之間的關(guān)系，公式為：

質(zhì)量 (mg) = 濃度 (mM) x 體積 (mL) x 分子摩爾量 (g/mol)

• pg ng μg mg g kg =
  fM pM nM μM mM M *
  nL μL mL L *