Background:

MDV3100, known as Enzalutamide, is a second-generation androgen receptor (AR) signaling inhibitor. It has been demonstrated impressive affinity to the AR compared to the first-generation AR inhibitors. It is able to inhibit binding of androgens to the AR, AR nuclear translocation, and the association of the AR with DNA. The AR is a 919-amino acid member of the steroid receptor transcription factor superfamily with different domains including an N-terminal regulation domain, a central DNA binding domain, and a C-terminal domain, which includes the ligand-binding domain incorporated within its protein structure. MDV3100 was identified by the Sawyers/Jung laboratories by using the nonsteroidal agonist. Testing was showing that it induced apoptosis in VCaP cells, an AR gene amplified human prostate cancer line, while bicalutamide was ineffective.

Reference

[1].Howard I. Scher, Karim Fizazi, Fred Saad, Mary-Ellen Taplin, Cora N. Sternberg, Kurt Miller, Ronald De Wit, Peter Mulders, Mohammad Hirmand, Bryan Selby, Johann Sebastian. Effect of MDV3100, an androgen receptor signaling inhibitor (ARSI), on overall survival in patients with prostate cancer postdocetaxel: Results from the phase III AFFIRM study. Journal of Clinical Oncology. 2012; 30(5):
[2].Manoj P. Menon, Celestia S. Higano. Enzalutamide, a Second Generation Androgen Receptor Antagonist: Development and Clinical Applications in Prostate Cancer. Current Oncology Reports. 2013; 15(2): 69 – 75.
[3].Joelle El-Amm, Nihar Patel, Ashley Freeman, Jeanny B. Aragon-Ching. Metastatic Castration-Resistant Prostate Cancer: Critical Review of Enzalutamide. Clinical Medicine Insights: Oncology. 2013; 7: 235 – 245.