The androgen receptor amino-terminal domain : structure, function and therapeutic potential

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Hunter, Irene and Jamieson, Craig and McEwan, Iain (2025) The androgen receptor amino-terminal domain : structure, function and therapeutic potential. Endocrine Oncology, 5 (1). e240061. (https://doi.org/10.1530/EO-24-0061)

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Abstract

Signalling by the steroid hormone testosterone involves the androgen receptor (AR), a structurally dynamic protein. The amino-terminal domain of the AR makes up more than half of the protein and has been found to be intrinsically disordered. This structural plasticity mediates receptor-dependent transcription, intradomain interactions and allosteric regulation. AR activity is a primary drug target in advanced and metastatic prostate cancer, a leading cause of cancer-related death in men. Recent research has focused on the amino-terminal domain as a novel drug target. In this review, we discuss the structural properties of the receptor and highlight some promising preclinical and clinical studies that aim to develop a drug discovery pipeline of small-molecule inhibitors targeting the amino-terminal domain.

ORCID iDs

Hunter, Irene, Jamieson, Craig ORCID logoORCID: https://orcid.org/0000-0002-6567-8272 and McEwan, Iain;
CORE (COnnecting REpositories)