6533b85efe1ef96bd12c0810

RESEARCH PRODUCT

Nonacidic Farnesoid X Receptor Modulators.

Markus HartmannDaniel FleschAstrid KaiserPascal HeitelJan S. KramerHartmut LüddensSun-yee CheungManfred Schubert-zsilaveczMario WurglicsJan HeeringDaniel MerkEwgenij ProschakJurema SchmidtMatthias GablerKerstin Lüddens-dämgenMara LindnerChristina Lamers

subject

0301 basic medicineMalemedicine.drug_classPyridinesPeroxisome proliferator-activated receptorReceptors Cytoplasmic and NuclearATP-binding cassette transporterCholesterol 7 alpha-hydroxylase01 natural sciencesRats Sprague-Dawley03 medical and health sciencesStructure-Activity RelationshipDrug StabilityDrug DiscoverymedicineGlucose homeostasisAnimalsHumansPPAR alphaReceptorCholesterol 7-alpha-HydroxylaseATP Binding Cassette Transporter Subfamily B Member 11chemistry.chemical_classificationBile acid010405 organic chemistryChemistryHEK 293 cellsImidazolesMembrane Transport ProteinsHep G2 Cells0104 chemical sciencesMolecular Docking SimulationZolpidem030104 developmental biologyHEK293 CellsBiochemistryMolecular MedicineFarnesoid X receptorATP-Binding Cassette TransportersSterol Regulatory Element Binding Protein 1HeLa Cells

description

As a cellular bile acid sensor, farnesoid X receptor (FXR) participates in regulation of bile acid, lipid and glucose homeostasis, and liver protection. Clinical results have validated FXR as therapeutic target in hepatic and metabolic diseases. To date, potent FXR agonists share a negatively ionizable function that might compromise their pharmacokinetic distribution and behavior. Here we report the development and characterization of a high-affinity FXR modulator not comprising an acidic residue.

yearjournalcountryeditionlanguage
2017-08-08Journal of medicinal chemistry
10.1021/acs.jmedchem.7b00903https://pubmed.ncbi.nlm.nih.gov/28749691