Verubecestat Trifluoroacetate

Product NameVerubecestat Trifluoroacetate
CAS2095432-65-6
MFC19H18F5N5O5S
MW523.44
EINECS
MOL File2095432-65-6.mol

Chemical Properties

storage temp.	under inert gas (nitrogen or Argon) at 2-8°C
solubility	DMSO: 81 mg/mL (154.75 mM);Ethanol: 5 mg/mL (9.55 mM)
Water Solubility	Water: Insoluble

Usage And Synthesis

Uses

Verubecestat (MK-8931) TFA is an orally active, high-affinity BACE1 and BACE2 inhibitor with Ki values of 2.2 nM and 0.38 nM. Verubecestat TFA effectively reduces Aβ40 and has the potential for Alzheimer's Disease[1][2].

Biological Activity

Verubecestat (MK-8931) Trifluoroacetat is a potent and selective beta-secretase inhibitor, a BACE1 inhibitor.

in vitro

Verubecestat(MK-8931) effectively reduces Aβ40 in cells, Ki：7.8 nM and IC50 ：13 nM.

in vivo

single oral dose of Verubecestat (MK-8931) to rats and cynomolgus monkeys significantly reduced cerebrospinal fluid (CSF) and cortical Aβ40. MK-8931 has an in vivo half-life of 20 hours, and is suitable for a once-daily dosing frequency.

target

Target	Value
BACE2 (Cell-free assay)	0.37 nM(Ki)
BACE1 (Cell-free assay)	1.75 nM(Ki)

References

[1] Yan R, et al. Stepping closer to treating Alzheimer's disease patients with BACE1 inhibitor drugs. Transl Neurodegener. 2016 Jul 14;5:13. DOI:10.1186/s40035-016-0061-5
[2] 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. DOI:10.1021/acs.jmedchem.6b00307