Year of Award
2026
Document Type
Professional Paper
Degree Type
Master of Science (MS)
Degree Name
Pharmaceutical Sciences and Drug Design
Department or School/College
Biomedical and Pharmaceutical Sciences
Committee Chair
Travis Hughes
Committee Co-chair
Kasper Hansen
Commitee Members
Philippe Diaz
Subject Categories
Biochemistry
Abstract
Nuclear receptors are transcription factors that bind ligands and recruit other coregulator proteins to initiate transcription on select genes. The farnesoid x receptor (FXR) is a nuclear receptor transcription factor that is a drug target for metabolic diseases such as primary biliary cholangitis and non-alcoholic fatty liver disease. However, current agonists targeting this receptor have revealed significant adverse effects in clinical trials limiting their use. Some agonists have shown different and less severe adverse effects compared to others in clinical data suggesting that not all agonists induce the same gene activation, but the mechanisms behind these differences are unknown. Here we investigate two FXR agonists, GW4064 and obeticholic acid, as ligand/receptor complexes and determined that obeticholic acid displays preferential binding or a bias for one coregulator protein compared to a different coregulator protein. However, when investigating longer lengths of these coregulator proteins, this bias does not occur. Further work will be necessary to determine if the bias mechanism is found in other FXR agonists and coregulator proteins and whether in vivo experiments suggest altered genetic responses between agonists.
Recommended Citation
Abel, Connor Douglas; Lott, Reece; and Hughes, Travis, "Evaluating Ligand-Induced Coregulator Bias in the Farnesoid x Receptor" (2026). Graduate Student Theses, Dissertations, & Professional Papers. 12725.
https://scholarworks.umt.edu/etd/12725
© Copyright 2026 Connor Douglas Abel, Reece Lott, and Travis Hughes