Abstract
The androgen receptor (AR) has been shown to be a key determinant in the pathogenesis of castration-resistant prostate cancer (CRPC). The current standard of care therapies targets the ligand-binding domain of the receptor and can afford improvements to life expectancy often only in the order of months before resistance occurs. Emerging preclinical and clinical compounds that inhibit receptor activity via differentiated mechanisms of action which are orthogonal to current antiandrogens show promise for overcoming treatment resistance. In this review, we present an authoritative summary of molecules that noncompetitively target the AR. Emerging small molecule strategies for targeting alternative domains of the AR represent a promising area of research that shows significant potential for future therapies. The overall quality of lead candidates in the area of noncompetitive AR inhibition is discussed, and it identifies the key chemotypes and associated properties which are likely to be, or are currently, positioned to be first in human applications.
Original language | English |
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Pages (from-to) | 1701-1747 |
Number of pages | 47 |
Journal | Medicinal Research Reviews |
Volume | 43 |
Issue number | 5 |
Early online date | 16 Apr 2023 |
DOIs | |
Publication status | Published - Sept 2023 |
Data Availability Statement
Data relating to calculated molecular properties of molecules reported in the review is available from the corresponding authors on request.Keywords
- androgen receptor
- developability properties
- noncompetitive inhibition
- prostate cancer