BioCentury
ARTICLE | Distillery Therapeutics

Therapeutics: Androgen receptor

October 13, 2016 7:00 AM UTC

Cell culture and mouse studies identified a peptoid-based androgen receptor antagonist that could help treat prostate cancers resistant to Xtandi enzalutamide and other androgen receptor antagonists. In multiple human prostate cancer cell lines, including those resistant to Xtandi and bicalutamide, a glycine oligomer-based peptoid conjugated to two ethisterone functional groups inhibited growth with EC50 values of 3.2-6.7 μM. In a human prostate cancer cell line resistant to Xtandi and ARN-509, the peptoid conjugate decreased colony formation compared with vehicle. In a xenograft mouse model of Xtandi- and ARN-509-resistant prostate cancer, the antagonist decreased tumor growth compared with vehicle. Next steps include optimizing the activity of the antagonist.

Pfizer Inc. and Astellas Pharma Inc. market Xtandi to treat prostate cancer and have the compound in Phase III testing to treat breast cancer and Phase II testing to treat liver cancer...