Leriglitazone

Last updated
Leriglitazone
Leriglitazone.svg
Clinical data
Other namesHydroxypioglitazone
ATC code
Identifiers
  • 5-[[4-[2-[5-(1-Hydroxyethyl)pyridin-2-yl]ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C19H20N2O4S
Molar mass 372.44 g·mol−1
3D model (JSmol)
  • CC(C1=CN=C(C=C1)CCOC2=CC=C(C=C2)CC3C(=O)NC(=O)S3)O
  • InChI=1S/C19H20N2O4S/c1-12(22)14-4-5-15(20-11-14)8-9-25-16-6-2-13(3-7-16)10-17-18(23)21-19(24)26-17/h2-7,11-12,17,22H,8-10H2,1H3,(H,21,23,24)
  • Key:OXVFDZYQLGRLCD-UHFFFAOYSA-N

Leriglitazone is a PPAR-gamma agonist and metabolite of the glitazone pioglitazone. It is developed for adrenomyeloneuropathy, and other neurodegenerative diseases. [1] [2] [3] [4]

Contents

Society and culture

In January 2024, the European Medicines Agency (EMA) recommended the refusal of the marketing authorization for leriglitazone (Nezglyal) requested by Minoryx Therapeutics S.L. [5] In May 2024, the EMA confirmed its recommendation to refuse marketing authorization for leriglitazone. [5] Leriglitazone was intended for the treatment of cerebral adrenoleukodystrophy. [5]

Related Research Articles

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Adrenoleukodystrophy (ALD) is a disease linked to the X chromosome. It is a result of fatty acid buildup caused by failure of peroxisomal fatty acid beta oxidation which results in the accumulation of very long chain fatty acids in tissues throughout the body. The most severely affected tissues are the myelin in the central nervous system, the adrenal cortex, and the Leydig cells in the testes. The long chain fatty acid buildup causes damage to the myelin sheath of the neurons of the brain, resulting in seizures and hyperactivity. Other symptoms include problems in speaking, listening, and understanding verbal instructions.

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The thiazolidinediones, abbreviated as TZD, also known as glitazones after the prototypical drug ciglitazone, are a class of heterocyclic compounds consisting of a five-membered C3NS ring. The term usually refers to a family of drugs used in the treatment of diabetes mellitus type 2 that were introduced in the late 1990s.

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References

  1. Musokhranova, Uliana; Grau, Cristina; Vergara, Cristina; Rodríguez-Pascau, Laura; Xiol, Clara; Castells, Alba A.; Alcántara, Soledad; Rodríguez-Pombo, Pilar; Pizcueta, Pilar; Martinell, Marc; García-Cazorla, Angels; Oyarzábal, Alfonso (26 October 2023). "Mitochondrial modulation with leriglitazone as a potential treatment for Rett syndrome". Journal of Translational Medicine. 21 (1): 756. doi: 10.1186/s12967-023-04622-5 . ISSN   1479-5876. PMC   10601217 . PMID   37884937.
  2. Pizcueta, Pilar; Vergara, Cristina; Emanuele, Marco; Vilalta, Anna; Rodríguez-Pascau, Laura; Martinell, Marc (6 February 2023). "Development of PPARγ Agonists for the Treatment of Neuroinflammatory and Neurodegenerative Diseases: Leriglitazone as a Promising Candidate". International Journal of Molecular Sciences. 24 (4): 3201. doi: 10.3390/ijms24043201 . ISSN   1422-0067. PMC   9961553 . PMID   36834611.
  3. Rodríguez-Pascau, Laura; Vilalta, Anna; Cerrada, Marc; Traver, Estefania; Forss-Petter, Sonja; Weinhofer, Isabelle; Bauer, Jan; Kemp, Stephan; Pina, Guillem; Pascual, Sílvia; Meya, Uwe; Musolino, Patricia L.; Berger, Johannes; Martinell, Marc; Pizcueta, Pilar (2 June 2021). "The brain penetrant PPARγ agonist leriglitazone restores multiple altered pathways in models of X-linked adrenoleukodystrophy". Science Translational Medicine. 13 (596). doi:10.1126/scitranslmed.abc0555. PMID   34078742. S2CID   235305143.
  4. Pandolfo, Massimo; Reetz, Kathrin; Darling, Alejandra; Rodriguez de Rivera, Francisco Javier; Henry, Pierre-Gilles; Joers, James; Lenglet, Christophe; Adanyeguh, Isaac; Deelchand, Dinesh; Mochel, Fanny; Pousset, Françoise; Pascual, Sílvia; Van den Eede, Delphine; Martin-Ugarte, Itziar; Vilà-Brau, Anna; Mantilla, Adriana; Pascual, María; Martinell, Marc; Meya, Uwe; Durr, Alexandra (December 2022). "Efficacy and Safety of Leriglitazone in Patients With Friedreich Ataxia: A Phase 2 Double-Blind, Randomized Controlled Trial (FRAMES)". Neurology: Genetics. 8 (6): e200034. doi:10.1212/NXG.0000000000200034. PMC   9747094 . PMID   36524101.
  5. 1 2 3 "Nezglyal EPAR". European Medicines Agency . 25 January 2024. Retrieved 3 February 2024.