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Introduction of Nonacidic Side Chains on 6-Ethylcholane Scaffolds in the Identification of Potent Bile Acid Receptor Agonists with Improved Pharmacokinetic Properties
- Source :
- Molecules, Volume 24, Issue 6, Molecules, Vol 24, Iss 6, p 1043 (2019)
- Publication Year :
- 2019
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2019.
-
Abstract
- As a cellular bile acid sensor, farnesoid X receptor (FXR) and the membrane G-coupled receptor (GPBAR1) participate in maintaining bile acid, lipid, and glucose homeostasis. To date, several selective and dual agonists have been developed as promising pharmacological approach to metabolic disorders, with most of them possessing an acidic conjugable function that might compromise their pharmacokinetic distribution. Here, guided by docking calculations, nonacidic 6-ethyl cholane derivatives have been prepared. In vitro pharmacological characterization resulted in the identification of bile acid receptor modulators with improved pharmacokinetic properties.
- Subjects :
- FXR agonist
Protein Conformation
Pharmaceutical Science
Receptors, Cytoplasmic and Nuclear
Analytical Chemistry
Receptors, G-Protein-Coupled
Cholane
chemistry.chemical_compound
0302 clinical medicine
Drug Discovery
Glucose homeostasis
Receptor
0303 health sciences
Bile acid
Molecular Structure
FXR agonists
steroidal scaffold
Hep G2 Cells
G protein-coupled bile acid receptor
bile acid receptor
Molecular Docking Simulation
Biochemistry
Chemistry (miscellaneous)
030220 oncology & carcinogenesis
Molecular Medicine
Bile acid receptors
Medicinal chemistry
Steroidal scaffolds
bile acid receptors
medicinal chemistry
steroidal scaffolds
medicine.drug_class
Article
lcsh:QD241-441
Bile Acids and Salts
03 medical and health sciences
Structure-Activity Relationship
lcsh:Organic chemistry
Metabolic Diseases
medicine
Humans
Physical and Theoretical Chemistry
030304 developmental biology
Organic Chemistry
Lipid Metabolism
In vitro
Glucose
HEK293 Cells
chemistry
Docking (molecular)
Cholanes
Farnesoid X receptor
Subjects
Details
- Language :
- English
- ISSN :
- 14203049
- Database :
- OpenAIRE
- Journal :
- Molecules
- Accession number :
- edsair.doi.dedup.....c24c0b58de091b4b0daa58dc1e34a1ce
- Full Text :
- https://doi.org/10.3390/molecules24061043