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• 产品描述： Verubecestat (MK-8931) is an orally active, high-affinity BACE1 and BACE2 inhibitor with Ki values of 2.2 nM and 0.38 nM. Verubecestat effectively reduces Aβ40 and has the potential for Alzheimer's Disease

• 靶点： Ki: 2.2 nM (BACE1) and 0.38 nM (BACE2)

• 体外研究： Verubecestat (MK-8931) is a β-site amyloid precursor protein cleaving enzyme 1/2 (BACE1/2) inhibitor. Verubecestat does not significantly inhibit human CYP isoforms 1A2, 2C9, 2C19, 2D6, and 3A4 (all IC50>40 μM), indicating that the compound is unlikely to be a perpetrator of CYP-mediated drug-drug interactions. Verubecestat has IC50s of 2.1 nM, 0.7 nM, 4.4 nM for Aβ1-40, Aβ1-42, sAPPβ in HEK293 APPSwe/Lon cells

• 体内研究： Verubecestat (MK-8931; 3 mg/kg; IV or oral) has a T1/2 of 1.9 hours, a CL of 46 mL/min/kg, a Vss of 5.4 L/kg, a C max of 0.27 μM and a AUC of 1.1 μM•h for Sprague-Dawley (SD) rats.Verubecestat (1 mg/kg; IV) has a T1/2 of 4.9 hours, a CL of 21 mL/min/kg, a Vss of 7.5 L/kg for cynomolgus monkeys.Verubecestat (1 mg/kg; IV) has a T1/2 of 9.7 hours, a CL of 4.3 mL/min/kg, a Vss of 2.7 L/kg for beagle dogs.Verubecestat (30 mg/kg; orally; BID for 5 days) causes a modest (1.4-fold) induction of CYP 3A1 activity but does not significantly alter the expression of CYPs 1A1, 1A2, 2B, 3A2, or 4A in rats.Verubecestat dose-dependently reduces CSF and cortex Aβ40 with ED50 values of 5 and 8 mg/kg, respectively, corresponding to unbound plasma EC50 values of 48 and 81 nM, respectively.Verubecestat (3 and 10 mg/kg; orally) reduces profound, sustained of CSF Aβ40 levels and has peak effects on CSF Aβ lowering (72 and 81% reduction at 3 and 10 mg/kg, respectively) 12 h after dosing. Animal Model: Sprague-Dawley (SD) rats Dosage: 3 mg/kg (Pharmacokinetic Analysis) Administration: IV or oral Result: Had a T1/2 of 1.9 hours, a CL of 46 mL/min/kg, a Vss of 5.4 L/kg, a Cmax of 0.27 μM and a AUC of 1.1 μM•h.

• 参考文献：
  1. Scott JD, et al. Discovery of the 3-Imino-1,2,4-thiadiazinane 1,1-Dioxide Derivative Verubecestat (MK-8931)-A β-Site Amyloid Precursor Protein Cleaving Enzyme 1 Inhibitor for the Treatment of Alzheimer'sDisease. Med Chem. 2016 Dec 8;59(23):10435-10450. 2. Yan R, et al. Stepping closer to treating Alzheimer's disease patients with BACE1 inhibitor drugs. Transl Neurodegener. 2016 Jul 14;5:13.

• 溶解性： soluble  in  DMSO

• 保存条件： -20℃

• 配置溶液浓度参考：
  

  	1mg	5mg	10mg
  1 mM	2.443 ml	12.213 ml	24.425 ml
  5 mM	0.489 ml	2.443 ml	4.885 ml
  10 mM	0.244 ml	1.221 ml	2.443 ml
  50 mM	0.049 ml	0.244 ml	0.489 ml

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本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系，公式为：

质量 (mg) = 浓度 (mM) x 体积 (mL) x 分子量 (g/mol)

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