生物活性

• 描述Estrogen is essential for growth and development of the mammary glands and has been associated with the promotion and growth of breast cancer. Estrogen exerts many of its effects via two nuclear estrogen receptors (ERs), ERα and ERβ^[3]. GDC-0810 is an orally bioavailable SERD (selective estrogen receptor degrader) which is a potent antagonist and degrader of both Erα and Erβ with IC₅₀ values of 6.1 nM and 8.8 nM, respectively. And the EC₅₀ value for Erα of GDC-0810 is 0.7 nM^[2]. In MCF7 cells GDC-0810 effectively antagonized E2-mediated transcriptional activation of an ER reporter construct and inhibited cell proliferation with nanomolar potency. In mice, GDC-0810 exhibited low clearance (11 mL/min/kg) and 61% oral bioavailability. In the MCF7 xenograft model, GDC-0810 displayed dose dependent efficacy. The 100 mg/kg/day dose caused tumor regressions similar to withdrawal of estrogen pellets at the start of dosing^[1]. In a tamoxifen-sensitive MCF-7 xenograft model, GDC-0810 (3 mg/kg, p.o.) showed substantial tumor-growth inhibition, while all animals showed tumor regression of more than 50% without weight loss at the highest dose of 100 mg/kg/day^[2].
• 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
  NCT02802670	Healthy Volunteers	Phase 1	Completed	-	United States, Wisconsin ... more >> Madison, Wisconsin, United States, 53704 Collapse <<
  NCT01823835	Breast Cancer	Phase 2	Active, not recruiting	March 28, 2019	United States, California ... more >> Ucsd Medical Center San Diego, California, United States, 92103-8465 United States, Connecticut Yale Cancer Center New Haven, Connecticut, United States, 06520 United States, Massachusetts Massachusetts General Hospital. Boston, Massachusetts, United States, 02114 Dana Farber Cancer Institute Boston, Massachusetts, United States, 02215 United States, Missouri Washington University Saint Louis, Missouri, United States, 63128 United States, New York Mount SInai Medical Center New York, New York, United States, 10029 Memorial Sloan Kettering Cancer Center New York, New York, United States, 10065 United States, North Carolina Carolinas Healthcare System Charlotte, North Carolina, United States, 28208 United States, Ohio University Hospitals Case Medical Center; Seidman Cancer Center Cleveland, Ohio, United States, 44106 United States, Tennessee Vanderbilt University Medical Center Nashville, Tennessee, United States, 37232 United States, Washington Seattle Cancer Care Alliance Seattle, Washington, United States, 98109 Korea, Republic of National Cancer Center Gyeonggi-do, Korea, Republic of, 10408 Seoul National University Hospital Seoul, Korea, Republic of, 03080 Severance Hospital, Yonsei University Health System; Pharmacy Seoul, Korea, Republic of, 03722 Korea University Guro Hospital Seoul, Korea, Republic of, 08308 Asan Medical Center. Seoul, Korea, Republic of, 138-736 Netherlands VU MEDISCH CENTRUM; Dept. of Medical Oncology Amsterdam, Netherlands, 1081 HV Universitair Medisch Centrum Groningen Groningen, Netherlands, 9713 GZ Spain Hospital Universitari Vall d'Hebron Barcelona, Spain, 08035 Centro Integral Oncologico Clara Campal (CIOCC); Dirección Médica Madrid, Spain, 28050 Hospital Clinico Universitario de Valencia Valencia, Spain, 46010 Collapse <<
  NCT02621957	Breast Cancer	Phase 1	Completed	-	United States, Florida ... more >> Daytona Beach, Florida, United States, 32117 Collapse <<

• 更多
• 参考文献

• [1] Joseph JD, Darimont B, Zhou W, et al. The selective estrogen receptor downregulator GDC-0810 is efficacious in diverse models of ER+ breast cancer. Elife. 2016;5:e15828.

  [2] Lai A, Kahraman M, Govek S, et al. Identification of GDC-0810 (ARN-810), an Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) that Demonstrates Robust Activity in Tamoxifen-Resistant Breast Cancer Xenografts. J Med Chem. 2015;58(12):4888-4904.

  [3] Haldosén LA, Zhao C, Dahlman-Wright K. Estrogen receptor beta in breast cancer. Mol Cell Endocrinol. 2014;382(1):665-672.