Selective PPARδ Modulators Improve Mitochondrial Function: Potential Treatment for Duchenne Muscular Dystrophy (DMD).
ACS Med Chem Lett
; 9(9): 935-940, 2018 Sep 13.
Article
in En
| MEDLINE
| ID: mdl-30258544
ABSTRACT
The X-ray structure of the previously reported PPARδ modulator 1 bound to the ligand binding domain (LBD) revealed that the amide moiety in 1 exists in the thermodynamically disfavored cis-amide orientation. Isosteric replacement of the cis-amide with five-membered heterocycles led to the identification of imidazole 17 (MA-0204), a potent, selective PPARδ modulator with good pharmacokinetic properties. MA-0204 was tested in vivo in mice and in vitro in patient-derived muscle myoblasts (from Duchenne Muscular Dystrophy (DMD) patients); 17 altered the expression of PPARδ target genes and improved fatty acid oxidation, which supports the therapeutic hypothesis for the study of MA-0204 in DMD patients.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
ACS Med Chem Lett
Year:
2018
Document type:
Article
Affiliation country:
United States