Calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide that functions as a vasodilator, has an important role in pain pathways, and has become a target for migraine treatment (1). The CGRP peptide is characterized by an N-terminal disulfide bond, an alpha-helical structure than plays a role in binding affinity, and an amine C-terminal (1,2). CGRP exists in alpha- and beta-isoforms encoded by genes CALCA (CALC I) and CALCB (CALC II), respectively (1,2). alphaCGRP and betaCGRP only differ by three amino acids, have greater than 90% homology, and each peptide has a theoretical molecular weight of ~3.8 kDa (1,2). alphaCGRP is the predominant peptide form and is expressed in regions of the central and peripheral nervous system, including sensory fibers and the trigeminal ganglia (1,2). Other members of the CGRP gene family includes adrenomedullin, and adrenomedullin 2 (intermedin), amylin, and calcitonin (1,2). When CGRP is released from nerve fibers and blood vessels, it binds a CGRP receptor complex (1-3). The receptor consists of G-protein coupled receptor calcitonin-like receptor (CLR) that is associated with an accessory protein receptor activity-modifying protein (RAMP) (2,3).

Signaling of CGRP and its receptor are involved in vasodilation, neurogenic inflammation, and peripheral sensitization of nociceptors, all of which relate to migraine pathophysiology (2-3). Studies have found that CGRP is both released during migraines and can also induce migraines (3-5). Under normal conditions CGRP levels are typical and neurotransmission is relative; however, migraine triggers including light and sound can increase CGRP levels, enhance neurotransmission, and alter the pain and sensory aversions associated with migraines (2). Given its role, CGRP and its receptor have been the target of many migraine therapeutics including small molecule agonists called gepants and monoclonal antibodies (3-5). Ubrogepant and Rimegepant, two small molecule CGRP receptor agonists, have been FDA approved while another agonist, Atogepant, is ongoing in clinical trials (3,5). Additionally, four monoclonal antibodies against either CGRP or its receptor that are used to block signaling have been FDA approved: Eptinezumab, Fremanezumab, Galcanezumab, and Erenumab (3-5).

References

1. Russell, F. A., King, R., Smillie, S. J., Kodji, X., & Brain, S. D. (2014). Calcitonin gene-related peptide: physiology and pathophysiology. Physiological reviews, 94(4), 1099-1142. https://doi.org/10.1152/physrev.00034.2013

2. Russo A. F. (2015). Calcitonin gene-related peptide (CGRP): a new target for migraine. Annual review of pharmacology and toxicology, 55, 533-552. https://doi.org/10.1146/annurev-pharmtox-010814-124701

3. Wattiez, A. S., Sowers, L. P., & Russo, A. F. (2020). Calcitonin gene-related peptide (CGRP): role in migraine pathophysiology and therapeutic targeting. Expert opinion on therapeutic targets, 24(2), 91-100. https://doi.org/10.1080/14728222.2020.1724285

4. Deen, M., Correnti, E., Kamm, K., Kelderman, T., Papetti, L., Rubio-Beltran, E., Vigneri, S., Edvinsson, L., Maassen Van Den Brink, A., & European Headache Federation School of Advanced Studies (EHF-SAS) (2017). Blocking CGRP in migraine patients - a review of pros and cons. The journal of headache and pain, 18(1), 96. https://doi.org/10.1186/s10194-017-0807-1

5. de Vries, T., Villal0n, C. M., & MaassenVanDenBrink, A. (2020). Pharmacological treatment of migraine: CGRP and 5-HT beyond the triptans. Pharmacology & therapeutics, 211, 107528. https://doi.org/10.1016/j.pharmthera.2020.107528

Long Name

Calcitonin Gene Related Peptide I

Alternate Names

a-CGRP, alpha-CGRP, CGRP 1, CGRP alpha, CGRP I

Gene Symbol

CALCA

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Product Specific Notices for CGRP1 Antibody (galcanezumab) [Alexa Fluor® 700]

Alexa Fluor (R) products are provided under an intellectual property license from Life Technologies Corporation. The purchase of this product conveys to the buyer the non-transferable right to use the purchased product and components of the product only in research conducted by the buyer (whether the buyer is an academic or for-profit entity). The sale of this product is expressly conditioned on the buyer not using the product or its components, or any materials made using the product or its components, in any activity to generate revenue, which may include, but is not limited to use of the product or its components: (i) in manufacturing; (ii) to provide a service, information, or data in return for payment; (iii) for therapeutic, diagnostic or prophylactic purposes; or (iv) for resale, regardless of whether they are resold for use in research. For information on purchasing a license to this product for purposes other than as described above, contact Life Technologies Corporation, 5791 Van Allen Way, Carlsbad, CA 92008 USA or outlicensing@lifetech.com. This conjugate is made on demand. Actual recovery may vary from the stated volume of this product. The volume will be greater than or equal to the unit size stated on the datasheet.

This product is for research use only and is not approved for use in humans or in clinical diagnosis. Primary Antibodies are guaranteed for 1 year from date of receipt.

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CGRP1 Antibody (galcanezumab) [Alexa Fluor® 700]

Novus Biologicals, part of Bio-Techne | Catalog # NBP3-28517AF700

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Background: CGRP1