Crisdesalazine (INN; developmental code name AAD-2004) is a microsomal prostaglandin E2 synthase-1 (mPGES-1) inhibitor and free radical scavenger which is under development for the treatment of Alzheimer's disease, amyotrophic lateral sclerosis (ALS), depressive disorders, Parkinson's disease, and spinal muscular atrophy.[1][2][3] It was also under development for the treatment of arthritis, diabetes, pain, and pancreatitis, but development for these indications was discontinued.[1] Crisdesalazine is also approved under the brand name GedaCure for treatment of dogs with canine cognitive dysfunction.[4]
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| Trade names | GedaCure |
| Other names | AAD-2004; AAD2004 |
| Drug class | Microsomal prostaglandin E2 synthase-1 (mPGES-1) inhibitor; Free radical scavenger |
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| Formula | C16H14F3NO3 |
| Molar mass | 325.287 g·mol−1 |
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Background
editThe drug was derived from salicylic acids like mesalazine (5-aminosalicylate), aspirin (acetylsalicylate), and sulfasalazine.[2] By inhibiting mPGES-1 (also known as prostaglandin E synthase (PTGES)), it blocks prostaglandin E2 production.[2][5] Crisdesalazine is described as having a dual action, additionally acting as a direct free radical scavenger.[2] Crisdesalazine is described as having anti-inflammatory, antioxidant, and neuroprotective effects.[3] It seems to have potentially superior therapeutic effects compared to nonsteroidal anti-inflammatory drugs (NSAIDs; or cyclooxygenase inhibitors) like ibuprofen, for instance having better selectivity and safety.[2][5]
As of February 2023, crisdesalazine is in phase 1 clinical trials for Alzheimer's disease, amyotrophic lateral sclerosis (ALS), depressive disorders, and Parkinson's disease and is in the preclinical stage of development for spinal muscular atrophy.[1] It was first described in the scientific literature in 2012.[6][3]
See also
editReferences
edit- ^ a b c "Crisdesalazine". AdisInsight. 21 February 2023. Retrieved 19 October 2024.
- ^ a b c d e Nango H, Tsuruta K, Miyagishi H, Aono Y, Saigusa T, Kosuge Y (June 2023). "Update on the pathological roles of prostaglandin E2 in neurodegeneration in amyotrophic lateral sclerosis". Translational Neurodegeneration. 12 (1): 32. doi:10.1186/s40035-023-00366-w. PMC 10278279. PMID 37337289.
- ^ a b c Dunkel P, Chai CL, Sperlágh B, Huleatt PB, Mátyus P (September 2012). "Clinical utility of neuroprotective agents in neurodegenerative diseases: current status of drug development for Alzheimer's, Parkinson's and Huntington's diseases, and amyotrophic lateral sclerosis". Expert Opinion on Investigational Drugs. 21 (9): 1267–1308. doi:10.1517/13543784.2012.703178. PMID 22741814.
- ^ "GNT Pharma's GedaCure® Approved for the Treatment of Dogs With Cognitive Dysfunction Syndrome". BioSpace. 10 February 2021. Retrieved 19 October 2024.
- ^ a b Pereira-Leite C, Nunes C, Jamal SK, Cuccovia IM, Reis S (July 2017). "Nonsteroidal Anti-Inflammatory Therapy: A Journey Toward Safety". Medicinal Research Reviews. 37 (4): 802–859. doi:10.1002/med.21424. PMID 28005273.
- ^ Lima IV, Bastos LF, Limborço-Filho M, Fiebich BL, de Oliveira AC (2012). "Role of prostaglandins in neuroinflammatory and neurodegenerative diseases". Mediators of Inflammation. 2012: 946813. doi:10.1155/2012/946813. PMC 3385693. PMID 22778499.