1. Development of a novel NURR1/NOT agonist from hit to lead and candidate for the potential treatment of Parkinson's disease.
- Author
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Lesuisse D, Malanda A, Peyronel JF, Evanno Y, Lardenois P, De-Peretti D, Abécassis PY, Barnéoud P, Brunel P, Burgevin MC, Cegarra C, Auger F, Dommergue A, Lafon C, Even L, Tsi J, Luc TPH, Almario A, Olivier A, Castel MN, Taupin V, Rooney T, and Vigé X
- Subjects
- Animals, Cell Line, Cricetinae, Drug Discovery, Gene Expression Regulation drug effects, Homeodomain Proteins metabolism, Interleukin-1beta genetics, Interleukin-1beta metabolism, Mice, Microglia drug effects, Molecular Structure, Neurons drug effects, Nuclear Receptor Subfamily 4, Group A, Member 2 genetics, Rats, Retinoid X Receptors genetics, Retinoid X Receptors metabolism, Neuroprotective Agents chemical synthesis, Neuroprotective Agents pharmacology, Nuclear Receptor Subfamily 4, Group A, Member 2 metabolism, Parkinson Disease drug therapy
- Abstract
In the course of a programme aimed at identifying Nurr1/NOT agonists for potential treatment of Parkinson's disease, a few hits from high throughput screening were identified and characterized. A combined optimization pointed to a very narrow and stringent structure activity relationship. A comprehensive program of optimization led to a potent and safe candidate drug displaying neuroprotective and anti-inflammatory activity in several in vitro and in vivo models., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Published
- 2019
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