生物活性

• 靶点	Androgen Receptor IC50:26nM

• 描述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].
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT03704519	Cerebrovascular Circulation	Phase 1	Recruiting	July 24, 2019	United Kingdom ... more >> Academic Neuroscience Centre, Kings College Recruiting London, United Kingdom, SE5 8AF Collapse <<
  NCT02363855	Prostatic Neoplasms	Phase 1	Completed	-	Japan ... more >> Kashiwa, Chiba, Japan, 277-8577 Collapse <<
  NCT03004534	Breast Cancer Female	Early Phase 1	Recruiting	April 2019	United States, California ... more >> UCLA Recruiting Los Angeles, California, United States, 90095-1678 Principal Investigator: Dennis Slamon, MD          Valley Breast Care and Women's Health Center Recruiting Los Angeles, California, United States, 91405 Principal Investigator: Thomas Lomis          Torrance Memorial Physician Network, Cancer Care Associates Recruiting Redondo Beach, California, United States, 90277 Principal Investigator: David Chan, MD          Central Coast Medical Oncology Completed Santa Maria, California, United States, 93454 United States, Florida UF Health Cancer Center - Orlando Health Completed Orlando, Florida, United States, 32806 Canada, Alberta Cross Cancer Institute Recruiting Edmonton, Alberta, Canada, T6G1Z2 Principal Investigator: John Mackey, MD          Canada, Quebec Centre Hospitalier de l'Université de Montréal (CHUM) Recruiting Montreal, Quebec, Canada, H2X 3E4 Principal Investigator: Andre Robidoux, MD          Jewish General Hospital Recruiting Montreal, Quebec, Canada, H3T1E2 Principal Investigator: Jean-Francois Boileau, MD          McGill University Hospital Recruiting Montreal, Quebec, Canada, H4A 3J1 Principal Investigator: Nathaniel Bouganim, MD          (CIUSSS) de l'Est-de-l'Île-de-Montréal - l'Hôpital Maisonneuve-Rosemont Completed Montréal, Quebec, Canada, H1T 2M4 Centre Hospitalier Affilie Universitaire De Quebec - Hospital Du Saint-Sacrement Recruiting Quebec City, Quebec, Canada, G1S 4L8 Principal Investigator: Louise Provencher, MD          Germany Universitatsklinikum Erlangen Recruiting Erlangen, Germany, 91054 Principal Investigator: Peter Fasching, MD          Interdisziplinares Onkologisches Zentrum Recruiting Muenchen, Germany, 80336 Principal Investigator: Wolfgang Eiermann, MD          Department of Women's Health Recruiting Tubingen, Germany, 72076 Principal Investigator: Andreas Hartkopf, MD Collapse <<

• 更多
• 参考文献

• [1] Moilanen AM, Riikonen R, Oksala R, et al. Discovery of ODM-201, a new-generation androgen receptor inhibitor targeting resistance mechanisms to androgen signaling-directed prostate cancer therapies. Sci Rep. 2015;5:12007

  [2] Fizazi K, Massard C, et al. Activity and safety of ODM-201 in patients with progressive metastatic castration-resistant prostate cancer (ARADES): an open-label phase 1 dose-escalation and randomised phase 2 dose expansion trial. Lancet Oncol. 2014 Aug;15(9):975-85.

  [3] Tan MH, Li J, Xu HE, Melcher K, Yong EL. Androgen receptor: structure, role in prostate cancer and drug discovery. Acta Pharmacol Sin. 2015; 36(1): 3‐23

  [4] Fizazi K, Albiges L, Loriot Y, et al. ODM-201: a new-generation androgen receptor inhibitor in castration-resistant prostate cancer. Expert Review of Anticancer Therapy, 2015, 15(9): 1007-1017