| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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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].
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| 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].
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| References |
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| Additional Infomation |
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.
Drug Indication For the treatment of migraine headaches. 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. 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. |
| 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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