NAV

Zavegepant

Identification

Generic Name
Zavegepant
DrugBank Accession Number
DB15688
Background

Zavegepant is an antagonist of the calcitonin gene-related peptide (CGRP) receptor currently in phase 3 trials in an intranasal formulation for the treatment of migraine. If FDA approved, it will join other previously-approved "-gepant" drugs rimegepant and ubrogepant as an additional treatment alternative for patients with migraine, particularly those for whom traditional triptan therapy has proven ineffective.

On April 15th, 2020, a phase 2 clinical trial (NCT04346615: Safety and Efficacy Trial of Vazegepant Intranasal for Hospitalized Patients With COVID-19 Requiring Supplemental Oxygen)1 began to investigate the use of intranasally administered zavegepant to combat the acute respiratory distress syndrome (ARDS) sometimes seen in patients with COVID-19. Acute lung injury activates the release of CGRP, which plays a role in the development of ARDS - CGRP antagonists, then, may help to blunt the significant inflammation associated with COVID-19.2 The clinical trial is expected to complete in September 2020.1

Type
Small Molecule
Groups
Investigational
Structure
3D
Similar Structures
Weight
Average: 638.817
Monoisotopic: 638.369287373
Chemical Formula
C36H46N8O3
Synonyms
  • 1-piperidinecarboxamide, 4-(1,2-dihydro-2-oxo-3-quinolinyl)-n-((1r)-1-((7-methyl-1h-indazol-5-yl)methyl)-2-(4-(1-methyl-4-piperidinyl)-1-piperazinyl)-2-oxoethyl)-
  • Vazegepant
  • Zavegepant
External IDs
  • BHV-3500
  • BMS-742413

Pharmacology

Indication

Not Available

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Contraindications & Blackbox Warnings
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Pharmacodynamics

Not Available

Mechanism of action
TargetActionsOrganism
ACalcitonin gene-related peptide type 1 receptor
antagonist
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
ODU3ZAZ94J
CAS number
1337918-83-8
InChI Key
JJVAPHYEOZSKJZ-JGCGQSQUSA-N
InChI
InChI=1S/C36H46N8O3/c1-24-19-25(20-28-23-37-40-33(24)28)21-32(35(46)43-17-15-42(16-18-43)29-9-11-41(2)12-10-29)39-36(47)44-13-7-26(8-14-44)30-22-27-5-3-4-6-31(27)38-34(30)45/h3-6,19-20,22-23,26,29,32H,7-18,21H2,1-2H3,(H,37,40)(H,38,45)(H,39,47)/t32-/m1/s1
IUPAC Name
N-[(2R)-3-(7-methyl-1H-indazol-5-yl)-1-[4-(1-methylpiperidin-4-yl)piperazin-1-yl]-1-oxopropan-2-yl]-4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxamide
SMILES
CN1CCC(CC1)N1CCN(CC1)C(=O)[C@@H](CC1=CC2=C(NN=C2)C(C)=C1)NC(=O)N1CCC(CC1)C1=CC2=C(NC1=O)C=CC=C2

References

General References
  1. NIH: Safety and Efficacy Trial of Vazegepant Intranasal for Hospitalized Patients With COVID-19 Requiring Supplemental Oxygen (NCT04346615) [Link]
  2. Practical Neurology: Vazegepant, Investigational Drug Being Studied for Migraine, to Enter Phase 2 Trial for COVID-19 Treatment [Link]
ChemSpider
30814207
ChEMBL
CHEMBL2397415
ZINC
ZINC000096271995

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentMigraine1
2, 3CompletedTreatmentAcute Migraine1
2, 3CompletedTreatmentMigraine1
2, 3RecruitingPreventionMigraine1
2, 3TerminatedTreatmentCoronavirus Disease 2019 (COVID‑19) / Covid 19 Infection1
1RecruitingTreatmentAsthma1

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 Solubility0.0696 mg/mLALOGPS
logP2.85ALOGPS
logP2.14Chemaxon
logS-4ALOGPS
pKa (Strongest Acidic)12.38Chemaxon
pKa (Strongest Basic)8.81Chemaxon
Physiological Charge1Chemaxon
Hydrogen Acceptor Count6Chemaxon
Hydrogen Donor Count3Chemaxon
Polar Surface Area116.91 Å2Chemaxon
Rotatable Bond Count6Chemaxon
Refractivity186.53 m3·mol-1Chemaxon
Polarizability71.32 Å3Chemaxon
Number of Rings7Chemaxon
Bioavailability1Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Targets

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Details1. Calcitonin gene-related peptide type 1 receptor
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Receptor for calcitonin-gene-related peptide (CGRP) together with RAMP1 and receptor for adrenomedullin together with RAMP3 (By similarity). Receptor for adrenomedullin together with RAMP2. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
Specific Function
Adrenomedullin receptor activity
Gene Name
CALCRL
Uniprot ID
Q16602
Uniprot Name
Calcitonin gene-related peptide type 1 receptor
Molecular Weight
52928.98 Da
References
  1. Mercer SE, Chaturvedula PV, Conway CM, Cook DA, Davis CD, Pin SS, Macci R, Schartman R, Signor LJ, Widmann KA, Whiterock VJ, Chen P, Xu C, Herbst JJ, Kostich WA, Thalody G, Macor JE, Dubowchik GM: Azepino-indazoles as calcitonin gene-related peptide (CGRP) receptor antagonists. Bioorg Med Chem Lett. 2021 Jan 1;31:127624. doi: 10.1016/j.bmcl.2020.127624. Epub 2020 Oct 21. [Article]
  2. Practical Neurology: Vazegepant, Investigational Drug Being Studied for Migraine, to Enter Phase 2 Trial for COVID-19 Treatment [Link]

Drug created at May 21, 2020 14:18 / Updated at May 06, 2022 10:06