This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Name
Verubecestat
Accession Number
DB12285  (DB08929)
Type
Small Molecule
Groups
Investigational
Description

Verubecestat is under investigation for the treatment of Alzheimer's Disease, Prodromal Alzheimer's disease, and Amnestic Mild Cognitive Impairment.

Verubecestat is Merck’s investigational oral β-site amyloid precursor protein cleaving enzyme (BACE1 or β secretase) inhibitor. In July 2013, Merck announced positive results for Phase Ib trials of Verubecestat. In the study, administration of Verubecestat at doses of 12, 40 and 60 mg resulted in a dose-dependent and sustained reduction in the levels of Ab40, a measure of BACE1 activity, in CSF from baseline of 57, 79 and 84 percent, respectively.

Structure
Thumb
Synonyms
Not Available
External IDs
MK-8931 / SCH 900931 / SCH-900931 / SCH900931
Categories
UNII
J1I0P6WT7T
CAS number
1286770-55-5
Weight
Average: 409.41
Monoisotopic: 409.102016927
Chemical Formula
C17H17F2N5O3S
InChI Key
YHYKUSGACIYRML-KRWDZBQOSA-N
InChI
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
IUPAC Name
N-{3-[(5R)-3-amino-2,5-dimethyl-1,1-dioxo-5,6-dihydro-2H-1lambda6,2,4-thiadiazin-5-yl]-4-fluorophenyl}-5-fluoropyridine-2-carboxamide
SMILES
CN1C(N)=N[C@@](C)(CS1(=O)=O)C1=CC(NC(=O)C2=CC=C(F)C=N2)=CC=C1F

Pharmacology

Indication
Not Available
Pharmacodynamics
Not Available
Mechanism of action

The amyloid hypothesis asserts that the formation of amyloid peptides that lead to amyloid plaque deposits in the brain is a primary contributor to the underlying cause of Alzheimer's disease. BACE is believed to be a key enzyme in the production of amyloid β peptide. Evidence suggests that inhibiting BACE decreases the production of amyloid β peptide and may therefore reduce amyloid plaque formation and modify disease progression.

TargetActionsOrganism
ABeta-secretase 1
inhibitor
Humans
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
Not Available

References

General References
Not Available
External Links
PubChem Compound
51352361
PubChem Substance
347828553
ChemSpider
31399364
BindingDB
47353
ChEMBL
CHEMBL3301601
ZINC
ZINC000144542146
PDBe Ligand
66F
Wikipedia
Verubecestat
PDB Entries
5hu1

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentAlzheimer's Disease (AD)2
1CompletedTreatmentAlzheimer's Disease (AD) / Amnestic Mild Cognitive Impairment / Prodromal Alzheimer's Disease1
2, 3TerminatedTreatmentAlzheimer's Disease (AD)1
3TerminatedTreatmentAlzheimer's Disease (AD) / Amnestic Mild Cognitive Impairment / Prodromal Alzheimer's Disease1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0367 mg/mLALOGPS
logP1.83ALOGPS
logP1.23ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)11.55ChemAxon
pKa (Strongest Basic)5.68ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area117.75 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity98.8 m3·mol-1ChemAxon
Polarizability38.39 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as aromatic anilides. These are aromatic compounds containing an anilide group in which the carboxamide group is substituted with an aromatic group. They have the general structure RNC(=O)R', where R= benzene, and R = aryl group.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Anilides
Direct Parent
Aromatic anilides
Alternative Parents
Pyridinecarboxamides / 2-heteroaryl carboxamides / Fluorobenzenes / Thiadiazines / Aryl fluorides / Organosulfonic acids and derivatives / Heteroaromatic compounds / Guanidines / Secondary carboxylic acid amides / Propargyl-type 1,3-dipolar organic compounds
show 7 more
Substituents
Aromatic anilide / Pyridinecarboxamide / Pyridine carboxylic acid or derivatives / 2-heteroaryl carboxamide / Fluorobenzene / Halobenzene / Aryl fluoride / Aryl halide / Pyridine / Thiadiazine
show 22 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Peptidase activity
Specific Function
Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves at the N-terminus of the A-beta peptide sequence, between residues 671 and 672 of APP, leads to the genera...
Gene Name
BACE1
Uniprot ID
P56817
Uniprot Name
Beta-secretase 1
Molecular Weight
55710.28 Da

Drug created on October 20, 2016 15:50 / Updated on March 01, 2020 21:09

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