Only in Titles

Search results for: AZD-3514 Mechanisms: Androgen Receptor antagonist

paperclip

#25708954   2015/02/21 To Up

Battling resistance mechanisms in antihormonal prostate cancer treatment: Novel agents and combinations.

Prostate cancer (PCa) is a hormone-sensitive disease. Androgen deprivation therapy lowers serum testosterone levels (castration) or blocks the androgen receptor (AR) ligand-binding domain. Especially in metastatic disease, hormonal therapy has been able to delay disease progression, reduce symptoms, and improve overall survival. Despite subsequent disease progression and development of castration resistance, PCa remains AR driven. Secondary hormonal treatments such as abiraterone acetate or enzalutamide have demonstrated increased overall survival. However, new resistance mechanisms to these agents have been identified, and systemic chemotherapy is still needed especially in fast-progressing castration-resistant PCa. Several promising androgen synthesis inhibitors (orteronel and galeterone), AR inhibitors (ARN-509, EPI-001, AZD3514, and ODM-201), and heat shock protein modulators (AT11387, 17-DMAG, STA-9090, and OGX-427) are currently under investigation. The wide variety in upcoming systemic agents underlines the molecular heterogeneity of castration-resistant PCa. This article reviews antihormonal therapy in PCa and resistance mechanisms and focuses on novel and upcoming agents currently in clinical testing.
Daan Joost De Maeseneer, Charles Van Praet, Nicolaas Lumen, Sylvie Rottey

2206 related Products with: Battling resistance mechanisms in antihormonal prostate cancer treatment: Novel agents and combinations.



Related Pathways

paperclip

#23861347   2013/07/16 To Up

AZD3514: a small molecule that modulates androgen receptor signaling and function in vitro and in vivo.

Continued androgen receptor (AR) expression and signaling is a key driver in castration-resistant prostate cancer (CRPC) after classical androgen ablation therapies have failed, and therefore remains a target for the treatment of progressive disease. Here, we describe the biological characterization of AZD3514, an orally bioavailable drug that inhibits androgen-dependent and -independent AR signaling. AZD3514 modulates AR signaling through two distinct mechanisms, an inhibition of ligand-driven nuclear translocation of AR and a downregulation of receptor levels, both of which were observed in vitro and in vivo. AZD3514 inhibited testosterone-driven seminal vesicle development in juvenile male rats and the growth of androgen-dependent Dunning R3327H prostate tumors in adult rats. Furthermore, this class of compound showed antitumor activity in the HID28 mouse model of CRPC in vivo. AZD3514 is currently in phase I clinical evaluation.
Sarah A Loddick, Sarah J Ross, Andrew G Thomason, David M Robinson, Graeme E Walker, Tom P J Dunkley, Sandra R Brave, Nicola Broadbent, Natalie C Stratton, Dawn Trueman, Elizabeth Mouchet, Fadhel S Shaheen, Vivien N Jacobs, Marie Cumberbatch, Joanne Wilson, Rhys D O Jones, Robert H Bradbury, Alfred Rabow, Luke Gaughan, Chris Womack, Simon T Barry, Craig N Robson, Susan E Critchlow, Stephen R Wedge, A Nigel Brooks

2858 related Products with: AZD3514: a small molecule that modulates androgen receptor signaling and function in vitro and in vivo.

100ug50 ug 100ul5mg2 Pieces/Box0.1 mg100ug100ul100ug50 ug 100ug50 ug

Related Pathways