Leriglitazone

Leriglitazone
Clinical data
Other names	Hydroxypioglitazone
ATC code	A16AX23 (WHO) ;
Identifiers
	IUPAC name 5-[[4-[2-[5-(1-Hydroxyethyl)pyridin-2-yl]ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione;
CAS Number	146062-44-4;
PubChem CID	4147757;
DrugBank	DB15021;
ChemSpider	3360070;
UNII	K824X25AYA;
KEGG	D11603;
ChEMBL	ChEMBL1267;
CompTox Dashboard (EPA)	DTXSID30399914 ;
Chemical and physical data
Formula	C19H20N2O4S
Molar mass	372.44 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC(C1=CN=C(C=C1)CCOC2=CC=C(C=C2)CC3C(=O)NC(=O)S3)O;
	InChI 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]

Society and culture

Legal status

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]

References

^ 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.
^ 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.
^ 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.
^ 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.
^ ^a ^b ^c "Nezglyal EPAR". European Medicines Agency. 25 January 2024. Retrieved 3 February 2024.

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[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.

[Nezglyal_EPAR-5] "Nezglyal EPAR". European Medicines Agency. 25 January 2024. Retrieved 3 February 2024.

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