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Details

Stereochemistry ABSOLUTE
Molecular Formula C17H17F2N5O3S
Molecular Weight 409.4121
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of VERUBECESTAT

SMILES

C[C@]1(CS(=O)(=O)N(C)C(=N)N1)c2cc(ccc2F)NC(=O)c3ccc(cn3)F

InChI

InChIKey=YHYKUSGACIYRML-KRWDZBQOSA-N
InChI=1S/C17H17F2N5O3S/c1-17(9-28(26,27)24(2)16(20)23-17)12-7-11(4-5-13(12)19)22-15(25)14-6-3-10(18)8-21-14/h3-8H,9H2,1-2H3,(H2,20,23)(H,22,25)/t17-/m0/s1

HIDE SMILES / InChI

Molecular Formula C17H17F2N5O3S
Molecular Weight 409.4121
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Verubecestat (MK 8931) is a potentially first-in-class, potent β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitor being developed by Merck. Verubecestat (MK-8931) is a selective, structurally unique BACE1 inhibitor that reduced plasma, cerebrospinal fluid (CSF), and brain concentrations of Aβ40, Aβ42, and sAPPβ (a direct product of BACE1 enzymatic activity) after acute and chronic administration to rats and monkeys. Verubecestat was under investigation for the treatment of Alzheimer's disease, prodromal Alzheimer's disease, and amnestic mild cognitive impairment. In November 2013, Merck began the APECS trial in 1,500 participants with prodromal AD, aka mild cognitive impairment due to AD (aMCI). These patients have measurable cognitive deficits and a positive PET scan with the newly FDA-approved amyloid tracer flutemetamol, but are not functionally impaired. APECS compared 12 and 40 mg once-daily doses to placebo; treatment was to last for two years. APECS usef change from baseline on the Clinical Dementia Rating Sum of Boxes (CDR-SB), a continuous measure, as its primary outcome. Secondary outcomes evaluated a range of newer measures, including a cognitive composite, CSF tau, brain imaging of hippocampal volume and amyloid load, and others. This trial was being conducted in more than 90 locations worldwide; it completed enrollment in November 2016 and was expected to complete data collection for its primary outcome in 2019. In February 2018, APECS was discontinued and Merck no longer listed verubecestat in its research pipeline. APECS participants on 40 mg verubecestat scored worse than the placebo group on the CDR-SB and ADAS-Cog13 starting at 13 weeks. The effect was small and did not progress over time. The 12 mg treatment group also performed slightly worse than controls, with the difference reaching significance at scattered time points.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
7.79999999999999982 nM [Ki]
PubMed

PubMed

TitleDatePubMed
Discovery of an Orally Available, Brain Penetrant BACE1 Inhibitor that Affords Robust CNS Aβ Reduction.
2012 Nov 8
Synthesis of Verubecestat, a BACE1 Inhibitor for the Treatment of Alzheimer's Disease.
2016 Nov 18
The BACE1 inhibitor verubecestat (MK-8931) reduces CNS β-amyloid in animal models and in Alzheimer's disease patients.
2016 Nov 2
Chronic Verubecestat Treatment Suppresses Amyloid Accumulation in Advanced Aged Tg2576-AβPPswe Mice Without Inducing Microhemorrhage.
2017
Drug candidates in clinical trials for Alzheimer's disease.
2017 Jul 19
Patents

Patents

Sample Use Guides

12, 40, or 60 mg/day of Verubecestat (MK 8931) given as once-daily tablets to placebo in people with mild to moderate AD.
Route of Administration: Oral
Substance Class Chemical
Created
by admin
on Fri Jun 25 23:31:14 UTC 2021
Edited
by admin
on Fri Jun 25 23:31:14 UTC 2021
Record UNII
J1I0P6WT7T
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
VERUBECESTAT
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
VERUBECESTAT [USAN]
Common Name English
VERUBECESTAT [INN]
Common Name English
SCH-900931
Code English
SCH900931
Code English
2-PYRIDINECARBOXAMIDE, N-(3-((5R)-3-AMINO-5,6-DIHYDRO-2,5-DIMETHYL-1,1-DIOXIDO-2H-1,2,4-THIADIAZIN-5-YL)-4-FLUOROPHENYL)-5-FLUORO-
Systematic Name English
SCH 900931
Code English
VERUBECESTAT [WHO-DD]
Common Name English
MK-8931
Code English
Classification Tree Code System Code
NCI_THESAURUS C471
Created by admin on Fri Jun 25 23:31:14 UTC 2021 , Edited by admin on Fri Jun 25 23:31:14 UTC 2021
NCI_THESAURUS C1509
Created by admin on Fri Jun 25 23:31:14 UTC 2021 , Edited by admin on Fri Jun 25 23:31:14 UTC 2021
Code System Code Type Description
NCI_THESAURUS
C152868
Created by admin on Fri Jun 25 23:31:14 UTC 2021 , Edited by admin on Fri Jun 25 23:31:14 UTC 2021
PRIMARY
EVMPD
SUB185177
Created by admin on Fri Jun 25 23:31:14 UTC 2021 , Edited by admin on Fri Jun 25 23:31:14 UTC 2021
PRIMARY
CAS
1286770-55-5
Created by admin on Fri Jun 25 23:31:14 UTC 2021 , Edited by admin on Fri Jun 25 23:31:14 UTC 2021
PRIMARY
FDA UNII
J1I0P6WT7T
Created by admin on Fri Jun 25 23:31:14 UTC 2021 , Edited by admin on Fri Jun 25 23:31:14 UTC 2021
PRIMARY
WIKIPEDIA
Verubecestat
Created by admin on Fri Jun 25 23:31:14 UTC 2021 , Edited by admin on Fri Jun 25 23:31:14 UTC 2021
PRIMARY
PUBCHEM
51352361
Created by admin on Fri Jun 25 23:31:14 UTC 2021 , Edited by admin on Fri Jun 25 23:31:14 UTC 2021
PRIMARY
ChEMBL
CHEMBL3301601
Created by admin on Fri Jun 25 23:31:14 UTC 2021 , Edited by admin on Fri Jun 25 23:31:14 UTC 2021
PRIMARY
INN
10028
Created by admin on Fri Jun 25 23:31:14 UTC 2021 , Edited by admin on Fri Jun 25 23:31:14 UTC 2021
PRIMARY
CAS
1613380-81-6
Created by admin on Fri Jun 25 23:31:14 UTC 2021 , Edited by admin on Fri Jun 25 23:31:14 UTC 2021
SUPERSEDED
DRUG BANK
DB12285
Created by admin on Fri Jun 25 23:31:14 UTC 2021 , Edited by admin on Fri Jun 25 23:31:14 UTC 2021
PRIMARY
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