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
- 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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- 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.
Target Actions Organism UCalcitonin gene-related peptide type 1 receptor antagonistHumans UCalcitonin gene-related peptide 1 Not Available 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
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- 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
- Amino Acids, Peptides, and Proteins
- Analgesics
- Calcitonin Gene-Related Peptide Receptor Antagonists
- Central Nervous System Agents
- Heterocyclic Compounds, Fused-Ring
- Oligopeptides
- Peptides
- Peripheral Nervous System Agents
- Receptors, Calcitonin Gene-Related Peptide, antagonists & inhibitors
- Sensory System Agents
- 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
- Recober A, Russo AF: Olcegepant, a non-peptide CGRP1 antagonist for migraine treatment. IDrugs. 2007 Aug;10(8):566-74. [Article]
- External Links
- 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
Phase Status Purpose Conditions Count 2 Completed Treatment Migraine 1 1 Completed Treatment Healthy 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
Property Value Source Water Solubility 0.0324 mg/mL ALOGPS logP 3.08 ALOGPS logP 1.62 Chemaxon logS -4.4 ALOGPS pKa (Strongest Acidic) 6.75 Chemaxon pKa (Strongest Basic) 10.21 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 8 Chemaxon Hydrogen Donor Count 5 Chemaxon Polar Surface Area 176.47 Å2 Chemaxon Rotatable Bond Count 12 Chemaxon Refractivity 214.28 m3·mol-1 Chemaxon Polarizability 84.7 Å3 Chemaxon Number of Rings 6 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9692 Blood Brain Barrier - 0.8022 Caco-2 permeable - 0.779 P-glycoprotein substrate Substrate 0.8342 P-glycoprotein inhibitor I Non-inhibitor 0.696 P-glycoprotein inhibitor II Non-inhibitor 0.8823 Renal organic cation transporter Non-inhibitor 0.8041 CYP450 2C9 substrate Non-substrate 0.8591 CYP450 2D6 substrate Non-substrate 0.7829 CYP450 3A4 substrate Non-substrate 0.5 CYP450 1A2 substrate Non-inhibitor 0.8027 CYP450 2C9 inhibitor Non-inhibitor 0.6565 CYP450 2D6 inhibitor Non-inhibitor 0.808 CYP450 2C19 inhibitor Non-inhibitor 0.6908 CYP450 3A4 inhibitor Non-inhibitor 0.6928 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7051 Ames test Non AMES toxic 0.6406 Carcinogenicity Non-carcinogens 0.8528 Biodegradation Not ready biodegradable 0.9946 Rat acute toxicity 2.2550 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.7242 hERG inhibition (predictor II) Inhibitor 0.8525
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets

- 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
- 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]
- 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]
- 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
- 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