Discovery of LOU064 (Remibrutinib), a Potent and Highly Selective Covalent Inhibitor of Bruton's Tyrosine Kinase.
Agammaglobulinaemia Tyrosine Kinase
/ antagonists & inhibitors
Animals
Benzamides
/ chemistry
Bridged Bicyclo Compounds, Heterocyclic
/ chemistry
Crystallography, X-Ray
/ methods
Dogs
Dose-Response Relationship, Drug
Drug Discovery
/ methods
Female
Humans
Mice
Protein Binding
/ physiology
Protein Kinase Inhibitors
/ chemistry
Protein Structure, Secondary
Protein Structure, Tertiary
Rats
Rats, Inbred Lew
Sheep
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:
28 05 2020
28 05 2020
Historique:
pubmed:
23
2
2020
medline:
24
10
2020
entrez:
22
2
2020
Statut:
ppublish
Résumé
Bruton's tyrosine kinase (BTK), a cytoplasmic tyrosine kinase, plays a central role in immunity and is considered an attractive target for treating autoimmune diseases. The use of currently marketed covalent BTK inhibitors is limited to oncology indications based on their suboptimal kinase selectivity. We describe the discovery and preclinical profile of LOU064 (remibrutinib,
Identifiants
pubmed: 32083858
doi: 10.1021/acs.jmedchem.9b01916
doi:
Substances chimiques
Benzamides
0
Bridged Bicyclo Compounds, Heterocyclic
0
CGI 1746
0
Protein Kinase Inhibitors
0
Agammaglobulinaemia Tyrosine Kinase
EC 2.7.10.2
BTK protein, human
EC 2.7.10.2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM