Year: 2010
Type: article
Abstract: The androgen receptor (AR) is critical for the growth and development of secondary sexual organs, muscle, bone and other tissues, making it an excellent therapeutic target.Ubiquitous expression of AR impedes the ability of endogenous steroids to function tissue selectively.In addition to the lack of tissue selectivity, clinical use of testosterone is limited due to poor bioavailability and pharmacokinetic problems.Our lab, in the last decade, discovered and developed tissue selective AR modulators (SARMs) that spare androgenic effects in secondary sexual organs, but demonstrate potential to treat muscle wasting diseases.This work reveals the discovery of next generation SARMs to treat prostate cancer and mechanistically characterize a prospective SARM in muscle and central nervous system (CNS).Prostate cancer relies on the AR for its growth, making it the primary therapeutic target in this disease.However, prolonged inhibition, with commercially available AR antagonists, leads to the development of mutations in its ligand binding domain resulting in resistance.Utilizing the crystal structure of AR-wild-type and AR-W741L mutant, we synthesized a series of AR pan-B.Duke III and Dong-Jin Hwang for synthesizing these wonderful compounds and discussions.I would like to thank my committee members, Drs.Thomas D. Schmittgen, William L. Hayton, and Robert W. Brueggemeier for their time and patience.I would also like to convey my deepest appreciation to Dr
Author: Amanda Jones
Institution: The Ohio State University
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2399376874