| Size | Price | Stock | Qty |
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| 5mg |
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| Targets |
The primary target of Olcegepant is the CGRP receptor (calcitonin gene-related peptide receptor). It acts as a selective and potent antagonist of the CGRP receptor with an IC50 of 0.03 nM and a Ki of 14.4 pM. By blocking the CGRP receptor, it prevents the activation of pain pathways associated with migraines. It binds to the human CGRP receptor with 150-fold higher affinity than the peptide antagonist CGRP8-37.
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| ln Vitro |
Olcegepant binds to the human CGRP receptor with a greater affinity than both the peptide antagonist CGRP8-37 and the natural ligand CGRP, by a factor of 150. Olcegepant reduces neurogenic vasodilation in animal surrogate models of migraine pathogenesis and reverses CGRP-mediated vasodilation in human cerebral arteries [1]. With an affinity (Ki) of 14.4±6.3 (n=4) pM for the human CGRP receptor, olegepant (BIBN4096BS) is incredibly potent against the primate CGRP receptor [2]. An innovative treatment for migraine may involve the use of calcitonin gene-related peptide (CGRP) receptor antagonists, according to a number of lines of evidence. The CGRP receptor found in SK-N-MC cells is competitively antagonistic to olegepant (BIBN4096BS). With sensitive myograph technology, the isolated human brain, coronary arteries, and omental arteries were investigated. Olcegepant competitively opposes the concentration-dependent relaxation that CGRP produces [3].
In vitro, Olcegepant binds to the human CGRP receptor with greater affinity than both the peptide antagonist CGRP8-37 and the natural ligand CGRP. It has an IC50 of 0.03 nM and a Ki of 14.4 pM. Its binding affinity and antagonistic activity are typically measured using radioligand binding assays and functional assays (e.g., cAMP accumulation) in cells expressing the CGRP receptor. |
| ln Vivo |
At doses ranging from 1 to 30 μg/kg (iv), olegepant (BIBN4096BS) suppresses the impact of CGRP produced from the trigeminal ganglion on marmosets' facial blood flow [2]. The whole trigeminal nucleus's capsaicin-induced Fos expression was 57% reduced by olegepant pretreatment (900 μg/kg). On the other hand, Olcegepant pretreatment had no effect on the expression of phosphorylated extracellular signal-regulated kinase in the trigeminal ganglia [4]. In CCI-ION rats, olegepant (0.3 to 0.9 mg/kg, intravenously) dramatically decreased mechanical allodynia. Olcegepant (0.6 mg/kg, i.v.) increased ATF3 transcripts, an indication of neuronal damage, and markedly decreased the amount of c-Fos immunolabeled cells in the trigeminal nerve's spinal nucleus, but not in the CCI trigeminal ganglion. Rats with interleukin-6 ION [5].
In vivo, Olcegepant reduced the severity of headache in 60% of migraine sufferers in a Phase II clinical trial. It met secondary endpoints including headache-free rate and rate of sustained response. It is well tolerated and does not display the vasoconstrictive effect that precludes the use of triptans in certain patients. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for Olcegepant involve radioligand binding studies using cell membranes expressing the human CGRP receptor. Competitive binding assays are performed using a radiolabeled CGRP ligand to determine the compound's affinity (Ki) for the receptor. Functional assays, such as measurement of cAMP accumulation, are used to assess its antagonist activity.
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| Cell Assay |
In vitro cellular assays for Olcegepant are conducted in cell lines expressing the CGRP receptor. Cells are treated with the compound, and its ability to inhibit CGRP-induced cAMP accumulation or calcium mobilization is measured. Its antagonist activity is quantified by measuring the shift in the dose-response curve of CGRP.
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| Animal Protocol |
In vivo animal studies for Olcegepant are conducted in animal models of migraine, such as the nitroglycerin-induced hyperalgesia model or the dural plasma protein extravasation model. The compound is administered orally or intravenously, and its effects on migraine-like symptoms are assessed. Its efficacy in reducing headache severity and other migraine symptoms is evaluated.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of Olcegepant indicate it has a molecular weight of 869.54 and a molecular formula of C38H47Br2N9O5. It is a non-peptide CGRP receptor antagonist. Its oral bioavailability and other PK parameters would be determined in preclinical and clinical studies. The compound is typically stored as a powder at appropriate conditions.
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| Toxicity/Toxicokinetics |
Toxicological information for Olcegepant is derived from clinical trials. It is well tolerated, with no significant vasoconstrictive effects. Common side effects may include nausea and dizziness. Its safety profile is favorable compared to triptans.
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| References |
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| Additional Infomation |
Boehringer Ingelheim's olcegepant (BIBN 4096) is a selective calcitonin gene-related peptide (CGRP) antagonist, belonging to a class of novel drugs under development for the treatment of acute migraine attacks. Olcegepant is currently undergoing Phase II clinical trials in Europe and the United States, and preliminary results suggest that CGRP antagonists may represent a potential new approach to treating migraines. Indications: For the treatment of migraines. Mechanism of Action: Migraines involve dysfunction of brainstem pathways that typically regulate sensory input. Clinical and experimental evidence supports the involvement of calcitonin gene-related peptide (CGRP) in the pathogenesis of migraines. CGRP and other neuropeptides released by the trigeminal nerve are thought to mediate neuroinflammation within the meninges, leading to severe brain pain during a migraine attack. CGRP antagonists, such as olcegepant, bind to CGRP receptors, blocking the action of CGRP and thus reducing inflammation.
Pharmacodynamics Ocegipam is a calcitonin gene-related peptide (CGRP) antagonist. In preclinical studies, oxegapam attenuated CGRP- or electrical stimulation-induced arterial dilation. In a phase II clinical trial, oxegapam reduced headache severity in 60% of migraine sufferers and met secondary endpoints including headache-free rate and sustained remission rate. Only mild to moderate transient adverse events were observed, and no adverse cardiovascular symptoms were reported. This compound appears to be an effective anti-migraine medication, well-tolerated, and does not produce vasoconstrictive effects like triptans and dihydroergotamine, thus avoiding contraindications in some patients. Olcegepant is a non-peptide CGRP receptor antagonist that was developed for the treatment of migraine. It is also known as BIBN4096BS. It was the first potent and selective non-peptide CGRP receptor antagonist. It showed efficacy in clinical trials for migraine. It is available from research chemical suppliers for research purposes. |
| Molecular Formula |
C38H47BR2N9O5
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| Molecular Weight |
869.66
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| Exact Mass |
867.207
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| CAS # |
204697-65-4
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| Related CAS # |
Olcegepant hydrochloride;586368-06-1
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| PubChem CID |
6918509
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| Appearance |
White to off-white solid powder
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| Vapour Pressure |
0mmHg at 25°C
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| LogP |
5.48
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
54
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| Complexity |
1250
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C1CN(CCC1N2CC3=CC=CC=C3NC2=O)C(=O)N[C@H](CC4=CC(=C(C(=C4)Br)O)Br)C(=O)N[C@@H](CCCCN)C(=O)N5CCN(CC5)C6=CC=NC=C6
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| InChi Key |
ITIXDWVDFFXNEG-JHOUSYSJSA-N
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| InChi Code |
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
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| Chemical Name |
N-[(2R)-1-[[(2S)-6-amino-1-oxo-1-(4-pyridin-4-ylpiperazin-1-yl)hexan-2-yl]amino]-3-(3,5-dibromo-4-hydroxyphenyl)-1-oxopropan-2-yl]-4-(2-oxo-1,4-dihydroquinazolin-3-yl)piperidine-1-carboxamide
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| Synonyms |
BIBN 4096; BIBN4096; BIBN-4096
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ≥ 50 mg/mL (~57.49 mM)
1M HCl : 50 mg/mL (~57.49 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (2.87 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (2.87 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (2.87 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 2.5 mg/mL (2.87 mM) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 5: 0.5 mg/mL (0.57 mM) in 1% DMSO 99% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.1499 mL | 5.7494 mL | 11.4987 mL | |
| 5 mM | 0.2300 mL | 1.1499 mL | 2.2997 mL | |
| 10 mM | 0.1150 mL | 0.5749 mL | 1.1499 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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