Androgen receptor (AR), is a member of the nuclear hormone receptor superfamily. AR is involved in sex development, reproductive system function, and androgen regulation. It regulates a variety of cellular events, proliferation, apoptosis, migration, invasion and differentiation. Prostate cancer cells generally depend on androgens for growth and survival. In general, tumor progression is inhibited by reducing the level of androgen in the body or inhibiting the androgen receptor, also known as androgen deprivation therapy (ADT). However, castration-resistant prostate cancer (CRPC) is resistant to ADT and produces androgen receptor variants, or androgen receptor mutations. Therefore, we introduce a potent AR antagonist JNJ-26146900, that effectively inhibits prostate cancer.

JNJ-26146900 is a potent and orally active androgen receptor antagonist.

In an animal model, JNJ-26146900 has a Ki of 400 nM for rat AR. Also binds rat androgen receptor transfected into Cos-7 cells with submicromolar potency. It also shows antitumor activity in vivo. Prevents prostate tumor growth in the Dunning rat model at doses of 30-100 mg/kg (p.o.). Also significantly inhibits tumor growth in the CWR22-LD1 mouse human prostate cancer xenograft model. Decreases the wet weight of the ventral prostate and levator ani muscles in adult male Sprague-Dawley rats at doses of 10-100 mg/kg (p.o.). Significantly reduces castration-induced tibial bone loss at a dose of 30 mg/kg. This activity of JNJ-26146900 is similar to that of the androgen antagonist Bicalutamide (HY-14249).

In conclusion, JNJ-26146900 can effectively antagonize AR, reduce prostate tumors and prevent bone loss.


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[2] Culig Z, et al. Cancer Metastasis Rev. 2014 Sep;33(2-3):413-27.