Olcegepant | BIBN-4096 | BIBN-4096BS | CAS#204697-65-4 | CGRP receptor antagonist

MedKoo Cat#: 326787 | Name: Olcegepant

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Olcegepant, also known as BIBN-4096 or BIBN-4096BS is is the first potent and selective non-peptide antagonist of the calcitonin gene-related peptide 1 (CGRP1) receptor, a key modulator in neurogenic inflammatory pain. 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. 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.

Chemical Structure

Olcegepant

CAS#204697-65-4

Theoretical Analysis

MedKoo Cat#: 326787

Name: Olcegepant

CAS#: 204697-65-4

Chemical Formula: C38H47Br2N9O5

Exact Mass: 867.2067

Molecular Weight: 869.66

Elemental Analysis: C, 52.48; H, 5.45; Br, 18.38; N, 14.50; O, 9.20

Price and Availability

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10mg	USD 625.00	2 Weeks

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Synonym

BIBN-4096; BIBN4096; BIBN 4096; BIBN-4096BS; BIBN4096BS; BIBN 4096BS; Olcegepant.

IUPAC/Chemical Name

N-((1R)-2-(((1S)-5-Amino-1-((4-(pyridin-4-yl)piperazin-1-yl)carbonyl)pentyl)amino)-1-(3,5-dibromo-4-hydroxybenzyl)-2-oxoethyl)-4-(2-oxo-1,4-dihydroquinazolin-3(2H)-yl)piperidine-1-carboxamide

InChi Key

ITIXDWVDFFXNEG-JHOUSYSJSA-N

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

SMILES Code

O=C(N1CCC(N2C(NC3=C(C=CC=C3)C2)=O)CC1)N[C@H](CC4=CC(Br)=C(O)C(Br)=C4)C(N[C@H](C(N5CCN(C6=CC=NC=C6)CC5)=O)CCCCN)=O

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

Olcegepant (BIBN-4096) is a potent and selective non-peptide antagonist of the calcitonin gene-related peptide 1 (CGRP1) receptor with IC50 of 0.03 nM and Ki of 14.4 pM.

In vitro activity:

IBN4096BS completely inhibited the specific binding of 125I-CGRP to SK-N-MC cells and displayed an affinity (Ki) of 14.4±6.3 pM (n=4) for the human CGRP receptor (Figure 2A). The endogenous ligand CGRP itself and the peptidic antagonist CGRP(8-37) displayed affinities (Ki) of 31.7±1.6 pM (n=15) and 3.6±0.7 nm (n=4), respectively. Employing the same cell line it was shown that BIBN4096BS is a pure antagonist. Reference: Br J Pharmacol. 2000 Feb;129(3):420-3. https://pubmed.ncbi.nlm.nih.gov/10711339/

In vivo activity:

Like naratriptan (0.1 to 0.3mg/kg, subcutaneously), olcegepant (0.3 to 0.9mg/kg, intravenously) markedly reduced mechanical allodynia in CCI-ION rats. In contrast, in CCI-SN rats, mechanical allodynia was completely unaffected and hyperalgesia was only marginally reduced by these drugs. A supra-additive antiallodynic effect was observed in CCI-ION rats treated with olcegepant (0.3mg/kg intravenously) plus naratriptan (0.1mg/kg subcutaneously), whereas this drug combination remained inactive in CCI-SN rats. Olcegepant (0.6mg/kg, intravenously) significantly reduced the number of c-Fos immunolabeled cells in spinal nucleus of the trigeminal nerve and upregulation of ATF3 transcript (a marker of neuron injury) but not that of interleukin-6 in trigeminal ganglion of CCI-ION rats. Reference: Pain. 2012 Sep;153(9):1939-1948. https://pubmed.ncbi.nlm.nih.gov/22795918/

	Solvent	mg/mL	mM
Solubility
	DMSO	50.0	57.49
	1M HCl	50.0	57.49

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 869.66 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Wang Y, Li Y, Wang M. Involvement of CGRP receptors in retinal spreading depression. Pharmacol Rep. 2016 Oct;68(5):935-8. doi: 10.1016/j.pharep.2016.05.001. Epub 2016 Jun 27. PMID: 27362770. 2. Doods H, Hallermayer G, Wu D, Entzeroth M, Rudolf K, Engel W, Eberlein W. Pharmacological profile of BIBN4096BS, the first selective small molecule CGRP antagonist. Br J Pharmacol. 2000 Feb;129(3):420-3. doi: 10.1038/sj.bjp.0703110. PMID: 10711339; PMCID: PMC1571877. 3. Kitagawa S, Tang C, Unekawa M, Kayama Y, Nakahara J, Shibata M. Sustained Effects of CGRP Blockade on Cortical Spreading Depolarization-Induced Alterations in Facial Heat Pain Threshold, Light Aversiveness, and Locomotive Activity in the Light Environment. Int J Mol Sci. 2022 Nov 9;23(22):13807. doi: 10.3390/ijms232213807. PMID: 36430285; PMCID: PMC9698572. 4. Michot B, Bourgoin S, Viguier F, Hamon M, Kayser V. Differential effects of calcitonin gene-related peptide receptor blockade by olcegepant on mechanical allodynia induced by ligation of the infraorbital nerve vs the sciatic nerve in the rat. Pain. 2012 Sep;153(9):1939-1948. doi: 10.1016/j.pain.2012.06.009. Epub 2012 Jul 15. PMID: 22795918.

In vitro protocol:

In vivo protocol:

1. Kitagawa S, Tang C, Unekawa M, Kayama Y, Nakahara J, Shibata M. Sustained Effects of CGRP Blockade on Cortical Spreading Depolarization-Induced Alterations in Facial Heat Pain Threshold, Light Aversiveness, and Locomotive Activity in the Light Environment. Int J Mol Sci. 2022 Nov 9;23(22):13807. doi: 10.3390/ijms232213807. PMID: 36430285; PMCID: PMC9698572. 2. Michot B, Bourgoin S, Viguier F, Hamon M, Kayser V. Differential effects of calcitonin gene-related peptide receptor blockade by olcegepant on mechanical allodynia induced by ligation of the infraorbital nerve vs the sciatic nerve in the rat. Pain. 2012 Sep;153(9):1939-1948. doi: 10.1016/j.pain.2012.06.009. Epub 2012 Jul 15. PMID: 22795918.

1: Rahman SM, Buchholz DW, Imbiakha B, Jager MC, Leach J, Osborn RM, Birmingham AO, Dewhurst S, Aguilar HC, Luebke AE. Migraine inhibitor olcegepant reduces weight loss and IL-6 release in SARS-CoV-2-infected older mice with neurological signs. J Virol. 2024 Jul 23;98(7):e0006624. doi: 10.1128/jvi.00066-24. Epub 2024 May 30. PMID: 38814068; PMCID: PMC11265435. 2: Rivera-Mancilla E, Al-Hassany L, Marynissen H, Bamps D, Garrelds IM, Cornette J, Danser AHJ, Villalón CM, de Hoon JN, MaassenVanDenBrink A. Functional Analysis of TRPA1, TRPM3, and TRPV1 Channels in Human Dermal Arteries and Their Role in Vascular Modulation. Pharmaceuticals (Basel). 2024 Jan 25;17(2):156. doi: 10.3390/ph17020156. PMID: 38399371; PMCID: PMC10892635. 3: de Vries T, Rubio-Beltrán E, van den Bogaerdt A, Dammers R, Danser AHJ, Snellman J, Bussiere J, MaassenVanDenBrink A. Pharmacology of erenumab in human isolated coronary and meningeal arteries: Additional effect of gepants on top of a maximum effect of erenumab. Br J Pharmacol. 2024 Jun;181(12):1720-1733. doi: 10.1111/bph.16322. Epub 2024 Feb 6. PMID: 38320397. 4: Younis S, Latysheva NV, Danilov AB, Ashina M. CGRP receptor antagonists (gepants). Handb Clin Neurol. 2024;199:51-66. doi: 10.1016/B978-0-12-823357-3.00033-1. PMID: 38307667. 5: Rahman SM, Luebke AE. Calcitonin gene-related peptide receptor antagonism reduces motion sickness indicators in mouse migraine models. Cephalalgia. 2024 Jan;44(1):3331024231223971. doi: 10.1177/03331024231223971. PMID: 38215227. 6: Xie X, Li Y, Yan B, Peng Q, Yao R, Deng Q, Li J, Wu Y, Chen S, Yang X, Ma P. Mediation of the JNC/ILC2 pathway in DBP-exacerbated allergic asthma: A molecular toxicological study on neuroimmune positive feedback mechanism. J Hazard Mater. 2024 Mar 5;465:133360. doi: 10.1016/j.jhazmat.2023.133360. Epub 2023 Dec 23. PMID: 38157815. 7: Rahman SM, Buchholz DW, Imbiakha B, Jaeger MC, Leach J, Osborn RM, Birmingham AO, Dewhurst S, Aguilar HC, Luebke AE. Migraine inhibitor olcegepant reduces weight loss and IL-6 release in SARS-CoV-2 infected older mice with neurological signs. bioRxiv [Preprint]. 2024 Jan 23:2023.10.23.563669. doi: 10.1101/2023.10.23.563669. Update in: J Virol. 2024 Jul 23;98(7):e0006624. doi: 10.1128/jvi.00066-24. PMID: 37965203; PMCID: PMC10634772. 8: Rahman SM, Guo L, Minarovich C, Moon L, Guo A, Luebke AE. Human RAMP1 overexpressing mice are resistant to migraine therapies for motion sensitivity: a mouse model of vestibular migraine. bioRxiv [Preprint]. 2023 Nov 28:2023.10.24.563838. doi: 10.1101/2023.10.24.563838. PMID: 37961568; PMCID: PMC10634789. 9: de Vries T, Boucherie DM, van den Bogaerdt A, Danser AHJ, MaassenVanDenBrink A. Blocking the CGRP Receptor: Differences across Human Vascular Beds. Pharmaceuticals (Basel). 2023 Jul 28;16(8):1075. doi: 10.3390/ph16081075. PMID: 37630989; PMCID: PMC10459004. 10: Landini L, Souza Monteiro de Araujo D, Chieca M, De Siena G, Bellantoni E, Geppetti P, Nassini R, De Logu F. Acetaldehyde via CGRP receptor and TRPA1 in Schwann cells mediates ethanol-evoked periorbital mechanical allodynia in mice: relevance for migraine. J Biomed Sci. 2023 Apr 26;30(1):28. doi: 10.1186/s12929-023-00922-6. PMID: 37101198; PMCID: PMC10131321. 11: Kitagawa S, Tang C, Unekawa M, Kayama Y, Nakahara J, Shibata M. Sustained Effects of CGRP Blockade on Cortical Spreading Depolarization-Induced Alterations in Facial Heat Pain Threshold, Light Aversiveness, and Locomotive Activity in the Light Environment. Int J Mol Sci. 2022 Nov 9;23(22):13807. doi: 10.3390/ijms232213807. PMID: 36430285; PMCID: PMC9698572. 12: Wee NKY, Novak S, Ghosh D, Root SH, Dickerson IM, Kalajzic I. Inhibition of CGRP signaling impairs fracture healing in mice. J Orthop Res. 2023 Jun;41(6):1228-1239. doi: 10.1002/jor.25474. Epub 2022 Oct 31. PMID: 36281531; PMCID: PMC10123175. 13: Greco R, Demartini C, Francavilla M, Zanaboni AM, Tassorelli C. Antagonism of CGRP Receptor: Central and Peripheral Mechanisms and Mediators in an Animal Model of Chronic Migraine. Cells. 2022 Sep 30;11(19):3092. doi: 10.3390/cells11193092. PMID: 36231054; PMCID: PMC9562879. 14: Wu S, Ren X, Zhu C, Wang W, Zhang K, Li Z, Liu X, Wang Y. A c-Fos activation map in nitroglycerin/levcromakalim-induced models of migraine. J Headache Pain. 2022 Sep 30;23(1):128. doi: 10.1186/s10194-022-01496-8. PMID: 36180824; PMCID: PMC9524028. 15: Oggero S, Cecconello C, Silva R, Zeboudj L, Sideris-Lampretsas G, Perretti M, Malcangio M. Dorsal root ganglia CX3CR1 expressing monocytes/macrophages contribute to arthritis pain. Brain Behav Immun. 2022 Nov;106:289-306. doi: 10.1016/j.bbi.2022.09.008. Epub 2022 Sep 14. PMID: 36115544; PMCID: PMC10166715. 16: Brabenec L, Hellenthal KEM, Müller M, Kintrup S, Zurek-Leffers F, Kardell M, Otto M, Wagner NM. Procalcitonin mediates vascular dysfunction in obesity. Life Sci. 2022 Oct 15;307:120889. doi: 10.1016/j.lfs.2022.120889. Epub 2022 Aug 20. PMID: 35998685. 17: Benbow T, Teja F, Sheikhi A, Exposto FG, Svensson P, Cairns BE. Peripheral N-methyl-D-aspartate receptor activation contributes to monosodium glutamate- induced headache but not nausea behaviours in rats. Sci Rep. 2022 Aug 16;12(1):13894. doi: 10.1038/s41598-022-18290-w. PMID: 35974090; PMCID: PMC9381496. 18: Viero FT, Rodrigues P, Frare JM, Da Silva NAR, Ferreira MA, Da Silva AM, Pereira GC, Ferreira J, Pillat MM, Bocchi GV, Nassini R, Geppetti P, Trevisan G. Unpredictable Sound Stress Model Causes Migraine-Like Behaviors in Mice With Sexual Dimorphism. Front Pharmacol. 2022 Jun 16;13:911105. doi: 10.3389/fphar.2022.911105. PMID: 35784726; PMCID: PMC9243578. 19: Argyriou AA, Mantovani E, Mitsikostas DD, Vikelis M, Tamburin S. A systematic review with expert opinion on the role of gepants for the preventive and abortive treatment of migraine. Expert Rev Neurother. 2022 Jun;22(6):469-488. doi: 10.1080/14737175.2022.2091435. Epub 2022 Jun 27. PMID: 35707907. 20: Kim MS, Kim BY, Saghetlians A, Zhang X, Okida T, Kim SY. Anti-nociceptive effects of dual neuropeptide antagonist therapy in mouse model of neuropathic and inflammatory pain. Korean J Pain. 2022 Apr 1;35(2):173-182. doi: 10.3344/kjp.2022.35.2.173. PMID: 35354680; PMCID: PMC8977203.