Androgen receptor splice variant 7 (AR-V7) N-terminal domain (AR-V7 NTD)

The Androgen receptor splice variant 7 (AR-V7) N-terminal domain is a key structural component of a truncated androgen receptor (AR) isoform that lacks the C-terminal ligand-binding domain (LBD) (Hu et al., 2009, Cancer Res). This variant is constitutively active and functions as a transcription factor that drives the expression of androgen-responsive genes even in the absence of circulating androgens (Myung et al., 2013, J Clin Invest). AR-V7 is a major mechanism of resistance to second-generation hormonal therapies like enzalutamide and abiraterone in patients with metastatic castration-resistant prostate cancer (mCRPC) (Antonarakis et al., 2014, N Engl J Med). The N-terminal domain (NTD) is an intrinsically disordered region containing the Activation Function 1 (AF-1), which is essential for the recruitment of transcriptional co-activators (De Mol et al., 2016, ACS Chem Biol). Because the NTD is conserved across both full-length AR and its splice variants, it represents a high-value therapeutic target for overcoming resistance (Le Moigne et al., 2020, Cancer Res). Drugs such as EPI-7386 are designed to bind the NTD and inhibit the transcriptional activity of all AR forms, offering a potential treatment for advanced prostate cancer (ESSA Pharma, 2023). Monitoring AR-V7 expression in circulating tumor cells serves as a significant biomarker for predicting poor response to LBD-targeted agents and guiding clinical decision-making (Scher et al., 2016, JAMA Oncol).

Other names

AR3Androgen receptor variant 7AR-V7Androgen receptor splice variant 7AR-V7 N-terminal domain

Direct binding to the N-terminal domain (NTD) of the androgen receptor, specifically the Activation Function 1 (AF-1) region, to inhibit its transcriptional activity by preventing the assembly of the transcriptional machinery and recruitment of co-activators (Myung et al., 2013, J Clin Invest; Le Moigne et al., 2020, Cancer Res).