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Verubecestat(MK-8931)
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Verubecestat(MK-8931)图片
CAS NO:1286770-55-5
包装与价格:
包装价格(元)
5mg电议
25mg电议
100mg电议
500mg电议
1g电议

产品介绍
Verubecestat (MK-8931) (MK-8931) 是一种具有口服活性的高亲和力 BACE1 和 BACE2 抑制剂,Ki 值为 2.2 nM 和 0.38 nM。
Cas No.1286770-55-5
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 SMILESO=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℃
General tipsFor obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.
Shipping ConditionEvaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request
产品描述

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.