Advances in the understanding of androgen receptor structure and function and in the development of next-generation AR-targeted therapeutics

被引:1
|
作者
Effah, Wendy [1 ]
Khalil, Marjana [1 ]
Hwang, Dong-Jin [2 ]
Miller, Duane D. [2 ]
Narayanan, Ramesh [1 ,3 ]
机构
[1] Univ Tennessee Hlth Sci Ctr, Coll Med, Dept Med, Memphis, TN 38163 USA
[2] Univ Tennessee Hlth Sci Ctr, Coll Pharm, Dept Pharmaceut Sci, Memphis, TN USA
[3] Univ Tennessee Hlth Sci Ctr, UTHSC Ctr Canc Res, Memphis, TN 38163 USA
关键词
Androgen receptor (AR); AR splice variants; Androgen receptor N -terminus; Selective AR degraders; Prostate cancer; Kennedy's disease; Condensates; LIQUID PHASE-SEPARATION; BULBAR MUSCULAR-ATROPHY; TRANSGENIC MOUSE MODEL; PROSTATE-CANCER; INSENSITIVITY SYNDROME; CLINICAL-IMPLICATIONS; TESTOSTERONE LEVELS; GENE-MUTATIONS; BREAST-CANCER; VARIANTS;
D O I
10.1016/j.steroids.2024.109486
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Androgen receptor (AR) and its ligand androgens are important for development and physiology of various tissues. AR and its ligands also play critical role in the development of various diseases, making it a valuable therapeutic target. AR ligands, both agonists and antagonists, are being widely used to treat pathological conditions, including prostate cancer and hypogonadism. Despite AR being studied widely over the last five decades, the last decade has seen striking advances in the knowledge on AR and discoveries that have the potential to translate to the clinic. This review provides an overview of the advances in AR biology, AR molecular mechanisms of action, and next generation molecules that are currently in development. Several of the areas described in the review are just unraveling and the next decade will bring more clarity on these developments that will put AR at the forefront of both basic biology and drug development.
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页数:9
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