JNJ-63576253 (free base)

JNJ-63576253 (TRC-253) free base is a potent and orally active full antagonist of androgen receptor (AR), with IC₅₀s of 37 and 54 nM for F877L mutant AR and wild-type AR in LNCaP cells. JNJ-63576253 free base can be used for the research of castration-resistant prostate cancer (CRPC)^[1]. IC50 & Target: IC50: 37 nM (F877L mutant AR in LNCaP cells); 54 nM (wild-type AR in LNCaP cells)^[1] In Vitro: JNJ-63576253 (0.0003-100 μM; 5 d) inhibits the growth of VCaP cells, with an IC₅₀ of 265 nM^[1].
JNJ-63576253 is stable in human liver microsomes, with an T_1/2 of >180 min^[1]. In Vivo: JNJ-63576253 (30 mg/kg; p.o. once daily for 72 days) significantly inhibits the growth of prostate LNCaP SRα F877L tumor in mice^[1].
JNJ-63576253 (30 mg/kg; p.o. once daily for 10 days) inhibits the five androgen sensitive organs (ASOs) under stimulation by testosterone propionate (TP) in mice^[1].
JNJ-63576253 (10 mg/kg; p.o.) exhibits moderate oral bioavailability (45%), C_max (0.66 μM) and AUC_last (4.9 μg?h/mL) in mice^[1].
JNJ-63576253 (2 mg/kg; i.v.) exhibits reasonable half-life (5.99 h), CL (15.0 mL/min/kg) and Vdss (6.11 L/kg) in mice^[1].