Discovery of MK-1468: A Potent, Kinome-Selective, Brain-Penetrant Amidoisoquinoline LRRK2 Inhibitor for the Potential Treatment of Parkinson's Disease.
Journal
Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531
Informations de publication
Date de publication:
09 11 2023
09 11 2023
Historique:
medline:
10
11
2023
pubmed:
20
10
2023
entrez:
20
10
2023
Statut:
ppublish
Résumé
Genetic mutation of the leucine-rich repeat kinase 2 (LRRK2) protein has been associated with Parkinson's disease (PD), a disabling and progressive neurodegenerative disorder that is devoid of efficacious disease-modifying therapies. Herein, we describe the invention of an amidoisoquinoline (IQ)-derived LRRK2 inhibitor lead chemical series. Knowledge-, structure-, and property-based drug design in concert with rigorous application of
Identifiants
pubmed: 37861679
doi: 10.1021/acs.jmedchem.3c01486
doi:
Substances chimiques
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
EC 2.7.11.1
Protein Kinase Inhibitors
0
Ion Channels
0
LRRK2 protein, human
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM