Crisdesalazine Explained

Tradename:GedaCure
Class:Microsomal prostaglandin E2 synthase-1 (mPGES-1) inhibitor; Free radical scavenger
Cas Number:927685-43-6
Pubchem:16042343
Drugbank:DB18405
Chemspiderid:13170885
Unii:11VWK61J69
Synonyms:AAD-2004; AAD2004
Iupac Name:2-hydroxy-5-[2-[4-(trifluoromethyl)phenyl]ethylamino]benzoic acid
C:16
H:14
F:3
N:1
O:3
Smiles:C1=CC(=CC=C1CCNC2=CC(=C(C=C2)O)C(=O)O)C(F)(F)F
Stdinchi:1S/C16H14F3NO3/c17-16(18,19)11-3-1-10(2-4-11)7-8-20-12-5-6-14(21)13(9-12)15(22)23/h1-6,9,20-21H,7-8H2,(H,22,23)
Stdinchikey:UTMVACIBQLDZLP-UHFFFAOYSA-N

Crisdesalazine (; 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] It was also under development for the treatment of arthritis, diabetes, pain, and pancreatitis, but development for these indications was discontinued. Crisdesalazine is also approved under the brand name GedaCure for treatment of dogs with canine cognitive dysfunction.[3]

Background

The drug was derived from salicylic acids like mesalazine (5-aminosalicylate), aspirin (acetylsalicylate), and sulfasalazine. By inhibiting mPGES-1 (also known as prostaglandin E synthase (PTGES)), it blocks prostaglandin E2 production.[4] Crisdesalazine is described as having a dual action, additionally acting as a direct free radical scavenger. Crisdesalazine is described as having anti-inflammatory, antioxidant, and neuroprotective effects. 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.

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. It was first described in the scientific literature in 2012.[5] [6]

See also

Notes and References

  1. Web site: Crisdesalazine . AdisInsight . 21 February 2023 . 19 October 2024.
  2. Nango H, Tsuruta K, Miyagishi H, Aono Y, Saigusa T, Kosuge Y . Update on the pathological roles of prostaglandin E2 in neurodegeneration in amyotrophic lateral sclerosis . Translational Neurodegeneration . 12 . 1 . 32 . June 2023 . 37337289 . 10278279 . 10.1186/s40035-023-00366-w . free .
  3. Web site: GNT Pharma's GedaCure® Approved for the Treatment of Dogs With Cognitive Dysfunction Syndrome . BioSpace . 10 February 2021 . 19 October 2024.
  4. Pereira-Leite C, Nunes C, Jamal SK, Cuccovia IM, Reis S . Nonsteroidal Anti-Inflammatory Therapy: A Journey Toward Safety . Medicinal Research Reviews . 37 . 4 . 802–859 . July 2017 . 28005273 . 10.1002/med.21424 .
  5. Lima IV, Bastos LF, Limborço-Filho M, Fiebich BL, de Oliveira AC . Role of prostaglandins in neuroinflammatory and neurodegenerative diseases . Mediators of Inflammation . 2012 . 946813 . 2012 . 22778499 . 3385693 . 10.1155/2012/946813 . free .
  6. Dunkel P, Chai CL, Sperlágh B, Huleatt PB, Mátyus P . 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 . September 2012 . 22741814 . 10.1517/13543784.2012.703178 .