NAV

Vafidemstat

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

Identification

Generic Name
Vafidemstat
DrugBank Accession Number
DB16446
Background

Vafidemstat is under investigation in clinical trial NCT03867253 (Testing the Safety and Preliminary Efficacy of the New Drug ORY-2001 in Mild to Moderate Alzheimer's Disease).

Type
Small Molecule
Groups
Investigational
Structure
3D
Similar Structures
Weight
Average: 336.395
Monoisotopic: 336.1586259
Chemical Formula
C19H20N4O2
Synonyms
  • Vafidemstat
External IDs
  • BCP29383
  • CS-0058593
  • HY-112623
  • ORY 2001
  • ORY-2001
  • ORY2001
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Pharmacology

Indication

Not Available

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Pharmacodynamics

Not Available

Mechanism of action

Vafidemstat is a small molecule irreversible inhibitor of histone demethylase LSD1 and also a dual inhibitor of LSD1/MAO-B.

TargetActionsOrganism
UAmine oxidase [flavin-containing] B
inhibitor
Humans
ULysine-specific histone demethylase 1A
inhibitor
binder
modulator
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

Adverse Effects
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Toxicity

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

Categories

Drug Categories
Classification
Not classified
Affected organisms
Not Available

Chemical Identifiers

UNII
LZ82JLT4UP
CAS number
1357362-02-7
InChI Key
XBBRLCXCBCZIOI-DLBZAZTESA-N
InChI
InChI=1S/C19H20N4O2/c20-19-23-22-18(25-19)11-21-17-10-16(17)14-6-8-15(9-7-14)24-12-13-4-2-1-3-5-13/h1-9,16-17,21H,10-12H2,(H2,20,23)/t16-,17+/m0/s1
IUPAC Name
5-({[(1R,2S)-2-[4-(benzyloxy)phenyl]cyclopropyl]amino}methyl)-1,3,4-oxadiazol-2-amine
SMILES
NC1=NN=C(CN[C@@H]2C[C@H]2C2=CC=C(OCC3=CC=CC=C3)C=C2)O1

References

General References
  1. Maes T, Mascaro C, Tirapu I, Estiarte A, Ciceri F, Lunardi S, Guibourt N, Perdones A, Lufino MMP, Somervaille TCP, Wiseman DH, Duy C, Melnick A, Willekens C, Ortega A, Martinell M, Valls N, Kurz G, Fyfe M, Castro-Palomino JC, Buesa C: ORY-1001, a Potent and Selective Covalent KDM1A Inhibitor, for the Treatment of Acute Leukemia. Cancer Cell. 2018 Mar 12;33(3):495-511.e12. doi: 10.1016/j.ccell.2018.02.002. Epub 2018 Mar 1. [Article]
  2. Fang Y, Liao G, Yu B: LSD1/KDM1A inhibitors in clinical trials: advances and prospects. J Hematol Oncol. 2019 Dec 4;12(1):129. doi: 10.1186/s13045-019-0811-9. [Article]
ChemSpider
68019508

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentBorderline Personality Disorder (BPD)1
2CompletedTreatmentMild to Moderate 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
logP1.97Chemaxon
pKa (Strongest Acidic)11.56Chemaxon
pKa (Strongest Basic)7.08Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count5Chemaxon
Hydrogen Donor Count2Chemaxon
Polar Surface Area86.2 Å2Chemaxon
Rotatable Bond Count7Chemaxon
Refractivity96.59 m3·mol-1Chemaxon
Polarizability37.52 Å3Chemaxon
Number of Rings4Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
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/MSsplash10-00kr-2629000000-b4a40e57ad43ed180b29
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-000l-0159000000-e4ac4e999bc64f7c8730
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-00di-4192000000-fde4e55a7282e564d411
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-00di-2590000000-ed64a938188ec6cf5ff1
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0006-9631000000-51009a50fbd256f30829
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-9742000000-a04979dcca02fbd04d37
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
Not Available

Targets

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Details1. Amine oxidase [flavin-containing] B
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Primary amine oxidase activity
Specific Function
Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral...
Gene Name
MAOB
Uniprot ID
P27338
Uniprot Name
Amine oxidase [flavin-containing] B
Molecular Weight
58762.475 Da
References
  1. Maes T, Mascaro C, Rotllant D, Lufino MMP, Estiarte A, Guibourt N, Cavalcanti F, Grinan-Ferre C, Pallas M, Nadal R, Armario A, Ferrer I, Ortega A, Valls N, Fyfe M, Martinell M, Castro Palomino JC, Buesa Arjol C: Modulation of KDM1A with vafidemstat rescues memory deficit and behavioral alterations. PLoS One. 2020 May 29;15(5):e0233468. doi: 10.1371/journal.pone.0233468. eCollection 2020. [Article]
Details2. Lysine-specific histone demethylase 1A
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Binder
Modulator
General Function
Histone demethylase that can demethylate both 'Lys-4' (H3K4me) and 'Lys-9' (H3K9me) of histone H3, thereby acting as a coactivator or a corepressor, depending on the context (PubMed:15620353, PubMed:15811342, PubMed:16140033, PubMed:16079794, PubMed:16079795, PubMed:16223729). Acts by oxidizing the substrate by FAD to generate the corresponding imine that is subsequently hydrolyzed (PubMed:15620353, PubMed:15811342, PubMed:16079794, PubMed:21300290). Acts as a corepressor by mediating demethylation of H3K4me, a specific tag for epigenetic transcriptional activation. Demethylates both mono- (H3K4me1) and di-methylated (H3K4me2) H3K4me (PubMed:15620353, PubMed:20389281, PubMed:21300290, PubMed:23721412). May play a role in the repression of neuronal genes. Alone, it is unable to demethylate H3K4me on nucleosomes and requires the presence of RCOR1/CoREST to achieve such activity (PubMed:16140033, PubMed:16079794, PubMed:16885027, PubMed:21300290, PubMed:23721412). Also acts as a coactivator of androgen receptor (AR)-dependent transcription, by being recruited to AR target genes and mediating demethylation of H3K9me, a specific tag for epigenetic transcriptional repression. The presence of PRKCB in AR-containing complexes, which mediates phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag that prevents demethylation H3K4me, prevents H3K4me demethylase activity of KDM1A (PubMed:16079795). Demethylates di-methylated 'Lys-370' of p53/TP53 which prevents interaction of p53/TP53 with TP53BP1 and represses p53/TP53-mediated transcriptional activation. Demethylates and stabilizes the DNA methylase DNMT1. Required for gastrulation during embryogenesis. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development. Effector of SNAI1-mediated transcription repression of E-cadherin/CDH1, CDN7 and KRT8. Required for the maintenance of the silenced state of the SNAI1 target genes E-cadherin/CDH1 and CDN7 (PubMed:20389281).
Specific Function
Androgen receptor binding
Gene Name
KDM1A
Uniprot ID
O60341
Uniprot Name
Lysine-specific histone demethylase 1A
Molecular Weight
92901.905 Da
References
  1. Antonijoan RM, Ferrero-Cafiero JM, Coimbra J, Puntes M, Martinez-Colomer J, Arevalo MI, Mascaro C, Molinero C, Buesa C, Maes T: First-in-Human Randomized Trial to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of the KDM1A Inhibitor Vafidemstat. CNS Drugs. 2021 Mar;35(3):331-344. doi: 10.1007/s40263-021-00797-x. Epub 2021 Mar 23. [Article]
  2. Maes T, Mascaro C, Rotllant D, Lufino MMP, Estiarte A, Guibourt N, Cavalcanti F, Grinan-Ferre C, Pallas M, Nadal R, Armario A, Ferrer I, Ortega A, Valls N, Fyfe M, Martinell M, Castro Palomino JC, Buesa Arjol C: Modulation of KDM1A with vafidemstat rescues memory deficit and behavioral alterations. PLoS One. 2020 May 29;15(5):e0233468. doi: 10.1371/journal.pone.0233468. eCollection 2020. [Article]

Drug created at January 20, 2021 04:53 / Updated at October 09, 2021 02:49