Verubecestat (MK-8931)
(Synonyms: 维罗司他; MK-8931) 目录号 : GC11098
An inhibitor of BACE1 and BACE2
Cas No.:1286770-55-5
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Ki: 2.2 and 3.4 nM for human and mouse Bace1, respectively
Verubecestat (MK-8931) is a BACE1 inhibitor.
β-Amyloid (Aβ) peptides are regarded to be involved in the etiology of AD. BACE1 is required for the Aβ production, and BACE1 inhibition is therefore an promising target for the AD treatment.
In vitro: Verubecestat has been identified as a potent inhibitor of both human and mouse Bace1 and verubecestat could also inhibit the production of Ab40, Ab42, and sAPPb in human cells with similar potency. Verubecestat was also found to be a potent inhibitor of purified human BACE2. Moreover, verubecestat was essentially inactive with over 45,000-fold selectivity in the purified human aspartyl proteases cathepsin D, cathepsin E, and pepsin and had a very weak inhibitor of purified human renin with 15,000-fold selectivity. In addition, verubecestat was also found to have minimal or no activity against various tested receptors, ion channels, transporters, as well as enzymes [1].
In vivo: Verubecestat could reduce plasma, cerebrospinal fluid, and brain concentrations of Aβ40, Aβ42, and sAPPβ after acute and chronic administration to both rats and monkeys. Moreover, the chronic treatment of rats and monkeys with verubecestat at exposures >40-fold higher than those tested in clinical trials did not cause many of the adverse effects previously reported to BACE inhibition. In rabbits and mice but not in monkeys, fur hypopigmentation was found [1].
Clinical trial: Single and multiple doses of verubecestat were generally well tolerated and produced reductions in Aβ40, Aβ42, and sAPPβ in the CSF [1].
Reference:
[1] Kennedy ME et al. The BACE1 inhibitor verubecestat (MK-8931) reduces CNS β-amyloid in animal models and in Alzheimer's disease patients. Sci Transl Med.2016 Nov 2;8(363):363ra150.
Cas No. | 1286770-55-5 | SDF | |
别名 | 维罗司他; MK-8931 | ||
化学名 | (R)-5-fluoro-N-(4-fluoro-3-(3-imino-2,5-dimethyl-1,1-dioxido-1,2,4-thiadiazinan-5-yl)phenyl)picolinamide 2,2,2-trifluoroacetate | ||
Canonical SMILES | O=C(C1=NC=C(F)C=C1)NC2=CC=C(F)C([C@@](C3)(C)NC(N(C)S3(=O)=O)=N)=C2.FC(F)(F)C(O)=O | ||
分子式 | C19H18F5N5O5S | 分子量 | 523.43 |
溶解度 | ≥ 40.9mg/mL in DMSO | 储存条件 | Store at -20°C |
General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效。 储备液的保存方式和期限:-80°C 储存时,请在 6 个月内使用,-20°C 储存时,请在 1 个月内使用。 为了提高溶解度,请将管子加热至37℃,然后在超声波浴中震荡一段时间。 |
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Shipping Condition | 评估样品解决方案:配备蓝冰进行发货。所有其他可用尺寸:配备RT,或根据请求配备蓝冰。 |
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1 mg | 5 mg | 10 mg |
1 mM | 1.9105 mL | 9.5524 mL | 19.1048 mL |
5 mM | 0.3821 mL | 1.9105 mL | 3.821 mL |
10 mM | 0.191 mL | 0.9552 mL | 1.9105 mL |
第一步:请输入基本实验信息(考虑到实验过程中的损耗,建议多配一只动物的药量) | ||||||||||
给药剂量 | mg/kg | 动物平均体重 | g | 每只动物给药体积 | ul | 动物数量 | 只 | |||
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% DMSO % % Tween 80 % saline | ||||||||||
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工作液浓度: mg/ml;
DMSO母液配制方法: mg 药物溶于 μL DMSO溶液(母液浓度 mg/mL,
体内配方配制方法:取 μL DMSO母液,加入 μL PEG300,混匀澄清后加入μL Tween 80,混匀澄清后加入 μL saline,混匀澄清。
1. 首先保证母液是澄清的;
2.
一定要按照顺序依次将溶剂加入,进行下一步操作之前必须保证上一步操作得到的是澄清的溶液,可采用涡旋、超声或水浴加热等物理方法助溶。
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