The androgen receptor (AR) belongs to the steroid hormone group of nuclear receptors with the estrogen receptor (ER), glucocorticoid receptor (GR), progesterone receptor (PR), and mineralocorticoid receptor (MR). Activation of androgen receptor (AR) is crucial for prostate cancer growth[3]. ODM-201 is a potent androgen receptor inhibitor with IC50 value of 26nM. In vitro, ODM-201 inhibited the androgen-induced nuclear translocation of overexpressed AR in HS-HEK293 cells. ODM-201 inhibited VCap cell proliferation with IC50 value of 230nM. However, ODM-201 had no effect on the viability of AR-negative tested, DU-145 prostate cancer cells and H1581 lung cancer cells[1].In vivo, oral administration of ODM-201 at 50mg/kg once or twice daily for 37 days significantly inhibited tumor growth in castrated (ORX) nude mice with subcutaneous VCap tumor [1]. After 7 days of oral administration with ODM-201 at 25~100mg/kg twice daily, blood: plasma levels for ODM-201 were 1.9–3.9% in mice, suggesting that the penetrance of ODM-201 through the blood brain barrier was negligible. Phase I/II clinical trial in men with mCRPC show that ODM-201 has promising anti-tumor activity in chemotherapy-pretreated patients[4].
作用机制
ODM-201 inhibits potently androgen binding to AR and androgen-induced nuclear translocation of AR[1].
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