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| Targets |
Olcegepant hydrochloride targets the calcitonin gene-related peptide 1 (CGRP1) receptor, a G protein-coupled receptor involved in vasodilation and pain transmission. The compound has an IC50 of 0.03 nM and a Ki of 14.4 pM for human CGRP. By antagonizing the CGRP1 receptor, olcegepant blocks CGRP-mediated vasodilation and neurogenic inflammation, key drivers of migraine pathophysiology.
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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 hydrochloride is a potent and selective non-peptide antagonist of the CGRP1 receptor with an IC50 of 0.03 nM and a Ki of 14.4 pM for human CGRP. The compound's high potency and selectivity for the CGRP1 receptor have been characterized in receptor binding and functional assays. It reverses CGRP-mediated vasodilation in human cerebral vessels. |
| 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 hydrochloride inhibits neurogenic vasodilation in surrogate animal models of migraine pathophysiology. The compound has been studied in preclinical models for its ability to block CGRP-mediated effects and reduce migraine-like symptoms. Its efficacy in animal models supports the role of CGRP in migraine and validates CGRP receptor antagonism as a therapeutic strategy. The compound was one of the first CGRP receptor antagonists to enter clinical development for migraine. |
| Enzyme Assay |
The in vitro receptor binding assay for olcegepant hydrochloride involves competition binding studies using membrane preparations from cells expressing the human CGRP1 receptor. Radiolabeled CGRP (e.g., ¹2⁵I-CGRP) is incubated with membrane preparations and varying concentrations of olcegepant (typically 0.001 pM to 10 uM) in binding buffer at room temperature for 1-2 hours. Bound and free ligand are separated by filtration through glass fiber filters, and radioactivity is measured by gamma counting. The inhibition constant (Ki) is calculated from IC50 values using the Cheng-Prusoff equation. Non-specific binding is determined in the presence of excess unlabeled CGRP.
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| Cell Assay |
In vitro cellular assays for olcegepant hydrochloride are conducted using cell lines expressing the human CGRP1 receptor. Cells are seeded in 96-well plates and treated with varying concentrations of olcegepant (typically 0.001 nM to 10 uM) in the presence or absence of CGRP. Receptor activation is assessed by measuring cAMP accumulation using a competitive immunoassay (e.g., AlphaScreen, HTRF, or ELISA). The antagonist potency (IC50 or Kb) is determined by assessing the compound's ability to inhibit CGRP-induced cAMP accumulation. Cell viability is monitored to ensure that observed effects are not due to cytotoxicity.
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| Animal Protocol |
In vivo animal studies for olcegepant hydrochloride typically involve administration to rodent models to assess its effects on CGRP-mediated vasodilation and migraine-like behaviors. The compound is administered by intravenous injection at doses ranging from 0.001-10 mg/kg. Neurogenic vasodilation is assessed in models such as the rat closed cranial window model or by measuring facial blood flow. The compound's ability to reverse CGRP-mediated vasodilation is measured. Behavioral endpoints such as light aversion or facial grimacing may be assessed in migraine models.
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| ADME/Pharmacokinetics |
Olcegepant hydrochloride has a molecular weight of 906.11 and a molecular formula of C38H47Br2N9O5·HCl. It is soluble in water at ≥66.66 mg/mL. The compound is available for research purposes only with high purity (99.39%). As a small molecule antagonist, it is expected to have good oral bioavailability and the ability to cross the blood-brain barrier. Detailed ADME parameters are documented in the primary literature on CGRP receptor antagonists.
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| Toxicity/Toxicokinetics |
The toxicological profile of olcegepant hydrochloride is characteristic of CGRP receptor antagonists. As a research compound, standard toxicity screening includes assessment of cytotoxicity in cell lines and evaluation of general toxicity parameters in animal models. The compound is for research use only and is not intended for human therapeutic use. No specific LD50 values have been reported. The compound should be handled with appropriate safety precautions in a laboratory setting.
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| References |
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| Additional Infomation |
Olcegepant hydrochloride (CAS 586368-06-1) is also known as BIBN-4096 hydrochloride. It is a potent and selective non-peptide antagonist of the CGRP1 receptor with an IC50 of 0.03 nM and a Ki of 14.4 pM for human CGRP. The compound reverses CGRP-mediated vasodilation in human cerebral vessels and inhibits neurogenic vasodilation in migraine models. It is a key research tool for studying the role of CGRP in migraine pathophysiology.
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| Molecular Formula |
C38H48BR2CLN9O5
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| Molecular Weight |
906.1060
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| Exact Mass |
905.181
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| CAS # |
586368-06-1
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| Related CAS # |
Olcegepant;204697-65-4
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| PubChem CID |
9919272
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| Appearance |
Light yellow to yellow solid powder
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| Hydrogen Bond Donor Count |
6
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
55
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| Complexity |
1250
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| Defined Atom Stereocenter Count |
2
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| SMILES |
BrC1C(=C(C([H])=C(C=1[H])C([H])([H])[C@]([H])(C(N([H])[C@@]([H])(C([H])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H])C(N1C([H])([H])C([H])([H])N(C2C([H])=C([H])N=C([H])C=2[H])C([H])([H])C1([H])[H])=O)=O)N([H])C(N1C([H])([H])C([H])([H])C([H])(C([H])([H])C1([H])[H])N1C(N([H])C2=C([H])C([H])=C([H])C([H])=C2C1([H])[H])=O)=O)Br)O[H].Cl[H]
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| InChi Key |
GJAWDDNZNYEKMO-XWIRJDCTSA-N
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| InChi Code |
InChI=1S/C38H47Br2N9O5.ClH/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);1H/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;hydrochloride
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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 : ~100 mg/mL (~110.36 mM)
H2O : ≥ 66.66 mg/mL (~73.57 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (5.52 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 50.0 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: ≥ 5 mg/mL (5.52 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 50.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 5 mg/mL (5.52 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.1036 mL | 5.5181 mL | 11.0362 mL | |
| 5 mM | 0.2207 mL | 1.1036 mL | 2.2072 mL | |
| 10 mM | 0.1104 mL | 0.5518 mL | 1.1036 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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