Year of Award

2019

Document Type

Thesis

Degree Type

Master of Science (MS)

Degree Name

Pharmaceutical Sciences

Department or School/College

Biomedical and Pharmaceutical Sciences

Committee Chair

Dr. Travis Hughes

Committee Co-chair

Dr. Philippe Diaz

Commitee Members

Dr. Nigel Priestley, Dr. Keith Parker

Keywords

PPAR, nTZDpa, NMP422, biased agonism

Subject Categories

Biochemistry | Biophysics | Medicinal-Pharmaceutical Chemistry | Organic Chemistry | Structural Biology

Abstract

Peroxisome proliferator-activated receptor gamma (PPARγ) has been a drug target to treat type 2 diabetes for the last 20 years when rosiglitazone and pioglitazone were approved by the FDA in 1999. While effective at increasing insulin sensitivity, these drugs cause serious adverse effects due to their full agonist characteristics. For that reason, drug discovery efforts have attempted to reduce or prevent the amount of agonist character of new PPARγ targeting ligands. Unfortunately, there have been no new FDA approved drugs for the receptor. There is a need for new ideas to produce better quality pharmaceuticals that lessen the impact of adverse effects. This work aims to propose and expand on new ideas: biased agonism and interactions that anchor a consistent binding mode.

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© Copyright 2019 Trey M. Patton