Back to Search
Start Over
Discovery of N-(3-Carbamoyl-5,5,7,7-tetramethyl-5,7-dihydro-4H-thieno[2,3-c]pyran-2-yl)-lH-pyrazole-5-carboxamide (GLPG1837), a Novel Potentiator Which Can Open Class III Mutant Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Channels to a High Extent
- Source :
- Journal of Medicinal Chemistry. 61:1425-1435
- Publication Year :
- 2018
- Publisher :
- American Chemical Society (ACS), 2018.
-
Abstract
- Cystic fibrosis (CF) is caused by mutations in the gene for the cystic fibrosis transmembrane conductance regulator (CFTR). With the discovery of Ivacaftor and Orkambi, it has been shown that CFTR function can be partially restored by administering one or more small molecules. These molecules aim at either enhancing the amount of CFTR on the cell surface (correctors) or at improving the gating function of the CFTR channel (potentiators). Here we describe the discovery of a novel potentiator GLPG1837, which shows enhanced efficacy on CFTR mutants harboring class III mutations compared to Ivacaftor, the first marketed potentiator. The optimization of potency, efficacy, and pharmacokinetic profile will be described.
- Subjects :
- 0301 basic medicine
congenital, hereditary, and neonatal diseases and abnormalities
Mutant
Pharmacology
medicine.disease_cause
Cystic fibrosis
Ivacaftor
03 medical and health sciences
0302 clinical medicine
Drug Discovery
medicine
Structure–activity relationship
Mutation
biology
Chemistry
Drug discovery
respiratory system
Potentiator
medicine.disease
digestive system diseases
Cystic fibrosis transmembrane conductance regulator
respiratory tract diseases
030104 developmental biology
030220 oncology & carcinogenesis
biology.protein
Molecular Medicine
medicine.drug
Subjects
Details
- ISSN :
- 15204804 and 00222623
- Volume :
- 61
- Database :
- OpenAIRE
- Journal :
- Journal of Medicinal Chemistry
- Accession number :
- edsair.doi...........dc1598dc3e22fb401aa0908c21814b75