NAV

Olcegepant

Identification

Generic Name
Olcegepant
DrugBank Accession Number
DB04869
Background

Boehringer Ingelheim Pharmaceuticals’ olcegepant (BIBN 4096) is a selective Calcitonin Gene-Related Peptide (CGRP) antagonist, a new class of drugs in development for the treatment of acute migraine attacks. Olcegepant is undergoing phase II trials in Europe and the US, with preliminary results suggesting that CGRP antagonists may represent a potential new approach to the treatment of migraine.

Type
Small Molecule
Groups
Investigational
Structure
Similar Structures
Weight
Average: 869.645
Monoisotopic: 867.206690953
Chemical Formula
C38H47Br2N9O5
Synonyms
  • Olcegepant
External IDs
  • BIBN 4096
  • BIBN 4096 BS
  • BIBN 4096BS
  • BIBN-4096 BS
  • BIBN-4096BS

Pharmacology

Indication

For the treatment of migraine headaches.

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Contraindications & Blackbox Warnings
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Pharmacodynamics

Olcegepant is a calcitonin gene-related peptide (CGRP) antagonist. In preclinical studies, olcegepant attenuated arterial dilation induced by CGRP or electrical stimulation. In a phase II clinical trial, olcegepant reduced the severity of headache in 60% of migraine sufferers and met secondary endpoints including headache-free rate and rate of sustained response. Only mild-to-moderate transient adverse events were observed, with no adverse cardiovascular symptoms reported. The compound appears to be an effective anti-migraine medication that is well tolerated and does not display the vasoconstrictive effect that precludes the use of triptans and dihydroergotamine in certain patients.

Mechanism of action

Migraine involves dysfunction of brainstem pathways that normally modulate sensory input. The involvement of calcitonin gene-related peptide (CGRP) in migraine pathology is supported by both clinical and experimental evidence. The release of CGRP and other neuropeptides from trigeminal nerves is thought to mediate neurogeate inflammation within the meninges which contributes to the generation of severe cerebral pain experienced during migraine attack. CGRP antagonists such as olcegepant bind at CGRP receptors, blocking the effect CGRP and thus reducing inflammation.

TargetActionsOrganism
UCalcitonin gene-related peptide type 1 receptor
antagonist
Humans
UCalcitonin gene-related peptide 1Not AvailableHumans
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
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as dipeptides. These are organic compounds containing a sequence of exactly two alpha-amino acids joined by a peptide bond.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Dipeptides
Alternative Parents
Tyrosine and derivatives / Phenylalanine and derivatives / N-acyl-alpha amino acids and derivatives / N-carbamoyl-alpha amino acids and derivatives / Alpha amino acid amides / N-arylpiperazines / Pyridinylpiperazines / Quinazolines / Amphetamines and derivatives / Piperidinecarboxamides
show 18 more
Substituents
1,4-diazinane / 1-piperidinecarboxamide / 2-bromophenol / 2-halophenol / Alpha-amino acid amide / Alpha-amino acid or derivatives / Alpha-dipeptide / Amine / Amino acid or derivatives / Aminopyridine
show 49 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
WOA5J8TX6M
CAS number
204697-65-4
InChI Key
ITIXDWVDFFXNEG-JHOUSYSJSA-N
InChI
InChI=1S/C38H47Br2N9O5/c39-29-21-25(22-30(40)34(29)50)23-33(45-37(53)48-15-10-28(11-16-48)49-24-26-5-1-2-6-31(26)44-38(49)54)35(51)43-32(7-3-4-12-41)36(52)47-19-17-46(18-20-47)27-8-13-42-14-9-27/h1-2,5-6,8-9,13-14,21-22,28,32-33,50H,3-4,7,10-12,15-20,23-24,41H2,(H,43,51)(H,44,54)(H,45,53)/t32-,33+/m0/s1
IUPAC Name
(2R)-N-[(2S)-6-amino-1-oxo-1-[4-(pyridin-4-yl)piperazin-1-yl]hexan-2-yl]-3-(3,5-dibromo-4-hydroxyphenyl)-2-{[4-(2-oxo-1,2,3,4-tetrahydroquinazolin-3-yl)piperidine-1-carbonyl]amino}propanamide
SMILES
NCCCC[C@H](NC(=O)[C@@H](CC1=CC(Br)=C(O)C(Br)=C1)NC(=O)N1CCC(CC1)N1CC2=C(NC1=O)C=CC=C2)C(=O)N1CCN(CC1)C1=CC=NC=C1

References

General References
  1. Recober A, Russo AF: Olcegepant, a non-peptide CGRP1 antagonist for migraine treatment. IDrugs. 2007 Aug;10(8):566-74. [Article]
PubChem Compound
6918509
PubChem Substance
175426877
ChemSpider
5293706
BindingDB
50184069
ChEMBL
CHEMBL207197
ZINC
ZINC000098052868
PDBe Ligand
3N6
Wikipedia
Olcegepant
PDB Entries
3n7r / 3n7s / 6zis

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentMigraine1
1CompletedTreatmentHealthy Subjects (HS)6

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0324 mg/mLALOGPS
logP3.08ALOGPS
logP1.62Chemaxon
logS-4.4ALOGPS
pKa (Strongest Acidic)6.75Chemaxon
pKa (Strongest Basic)10.21Chemaxon
Physiological Charge1Chemaxon
Hydrogen Acceptor Count8Chemaxon
Hydrogen Donor Count5Chemaxon
Polar Surface Area176.47 Å2Chemaxon
Rotatable Bond Count12Chemaxon
Refractivity214.28 m3·mol-1Chemaxon
Polarizability84.7 Å3Chemaxon
Number of Rings6Chemaxon
Bioavailability0Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9692
Blood Brain Barrier-0.8022
Caco-2 permeable-0.779
P-glycoprotein substrateSubstrate0.8342
P-glycoprotein inhibitor INon-inhibitor0.696
P-glycoprotein inhibitor IINon-inhibitor0.8823
Renal organic cation transporterNon-inhibitor0.8041
CYP450 2C9 substrateNon-substrate0.8591
CYP450 2D6 substrateNon-substrate0.7829
CYP450 3A4 substrateNon-substrate0.5
CYP450 1A2 substrateNon-inhibitor0.8027
CYP450 2C9 inhibitorNon-inhibitor0.6565
CYP450 2D6 inhibitorNon-inhibitor0.808
CYP450 2C19 inhibitorNon-inhibitor0.6908
CYP450 3A4 inhibitorNon-inhibitor0.6928
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7051
Ames testNon AMES toxic0.6406
CarcinogenicityNon-carcinogens0.8528
BiodegradationNot ready biodegradable0.9946
Rat acute toxicity2.2550 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7242
hERG inhibition (predictor II)Inhibitor0.8525
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

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

Targets

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Details1. Calcitonin gene-related peptide type 1 receptor
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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. Walker CS, Raddant AC, Woolley MJ, Russo AF, Hay DL: CGRP receptor antagonist activity of olcegepant depends on the signalling pathway measured. Cephalalgia. 2017 Jan 1:333102417691762. doi: 10.1177/0333102417691762. [Article]
  2. Liu J, Liu L, Zhao M, Ding N, Ge N, Daugherty SL, Beckel JM, Wang S, Zhang X: Activation of TRPM8 channel inhibits contraction of the isolated human ureter. Neurourol Urodyn. 2021 Aug;40(6):1450-1459. doi: 10.1002/nau.24689. Epub 2021 May 20. [Article]
Details2. Calcitonin gene-related peptide 1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Receptor binding
Specific Function
CGRP induces vasodilation. It dilates a variety of vessels including the coronary, cerebral and systemic vasculature. Its abundance in the CNS also points toward a neurotransmitter or neuromodulato...
Gene Name
CALCA
Uniprot ID
P06881
Uniprot Name
Calcitonin gene-related peptide 1
Molecular Weight
13897.755 Da
References
  1. Recober A, Russo AF: Olcegepant, a non-peptide CGRP1 antagonist for migraine treatment. IDrugs. 2007 Aug;10(8):566-74. [Article]

Drug created at October 20, 2007 10:10 / Updated at May 05, 2022 17:22