生物活性

• 描述The estrogen-related receptors (ERRs) comprise a small group of orphan nuclear receptor transcription factors. The ERRα and ERRγ isoforms play a central role in the regulation of metabolic genes and cellular energy metabolism. ERRβ is the important in the maintenance of embryonic stem cell pluripotency^[1]. The selective ERβ agonist AC-186 was evaluated in a rat model of Parkinson's disease induced through bilateral 6-hydroxydopamine lesions of the substantia nigra. In this model, AC-186 prevented motor, cognitive, and sensorimotor gating deficits and mitigated the loss of dopamine neurons in the substantia nigra, in males, but not in females. Furthermore, in male rats, 17β-estradiol, which activates ERβ and ERα with equal potency, did not show the same neuroprotective benefits as AC-186^[2].In male rats,AC-186 provided essentially complete reversal of Taxol-induced allodynia at doses of 10 and 30 mg/kg. Repeat dosing experiments showed that no tolerance or desensitization to the effects of AC-186 occurred over 5 days. The analgesic effects of AC-186 were blocked by the ERβ-selective antagonist PHTPP, and coadministration of an ERα-selective agonist (PPT)^[3].When ACP-105 is administered in combination with AC-186, they increase the amyloid-β degrading enzymes neprilysin and insulin-degrading enzyme and decrease amyloid-β levels in the brain as well as improve cognition. Interestingly, the androgen receptor level in the brain was increased by chronic treatment with the same combination treatment, ACP-105 and AC-186, not seen with DHT or ACP-105 alone^[4].
• 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
  NCT00289380	-	-	Recruiting	January 2020	China, Beijing ... more >> Beijing Friendship Hospital, Capital Medical University Active, not recruiting Beijing, Beijing, China, 100730 Peking Union Medical College Hospital Active, not recruiting Beijing, Beijing, China, 100730 China, Chongqing Chongqing Medical Univ. Hospital Completed Chongqing, Chongqing, China Xin Qiao Hospital Recruiting Chongqing, Chongqing, China Contact: Hua Yang, M.D.    +86 13668057773    hyang@med.umich.edu    Principal Investigator: Hua Yang, M.D.          China, Guangdong The First Affiliated Hospital, Sun Yat-sen University Recruiting Guangzhou, Guangdong, China, 510080 Contact: Wen-hua Zhan, M.D.    +86 20 87755766    wenhuazhan@medmail.com.cn    Principal Investigator: Wen-hua Zhan, M.D.          Sub-Investigator: Xiao-qing Liu, M.D.          China, Guangxi The First Affiliated Hospial, Guangxi Medical University Recruiting Nanning, Guangxi, China, 530021 Contact: Ning Xia, M.D.    +86 771 5303201       Principal Investigator: Ning Xia, M.D.          China, Hebei The First University Hospital, Hebei Medical University Recruiting Shijiazhuang, Hebei, China, 050031 Contact: Ru-mei Jia, M.D.    +86 311 85917000    jiarm@jyyy.com.cn    Principal Investigator: Ru-mei Jia, M.D.          Nankai Hospital Active, not recruiting Tianjin, Hebei, China, 300100 China, Hubei Tongji Hospital, Huazhong University of Science and Technology Recruiting Wuhan, Hubei, China, 430030 Contact: Yi-ping Wu, M.D.    +86 27 62363420    mail@tjh.tjmu.edu.cn    Principal Investigator: Yi-ping Wu, M.D.          China, Jiangsu Nanjing General Hospital of Nanjing Military Command Recruiting Nanjing, Jiangsu, China, 210002 Contact: Zhi-wei Jiang, M.D.    +86 25 84619727    surgery34@163.com    Principal Investigator: Zhi-wei Jiang, M.D.          China, Shanghai Xin Hua Hospital, Shanghai Jiaotong University Recruiting Shanghai, Shanghai, China, 200029 Contact: Wei Cai, M.D.    +86 21 65790000    caiwei204@yahoo.com.cn    Principal Investigator: Wei Cai, M.D.          Sixth Hospital Recruiting Shanghai, Shanghai, China Contact: Huai-Long Qin, M.D.       hlqin@sjtu.edu.cn    Sub-Investigator: Huai-Long Qin, M.D.          China, Xinjiang The First Affiliated Hospital, Xinjiang Medical University Active, not recruiting Urumqi, Xinjiang, China, 830054 China, Zhejiang Second Affiliated Hospital, Zhejiang University Active, not recruiting Hangzhou, Zhejiang, China, 310006 Collapse <<
  NCT02798120	Acne Vulgaris	Phase 3	Completed	-	-
  NCT03705507	Acute Lymphoblastic Leukemia ... more >> Acute Lymphoblastic Leukemia, Adult Acute Lymphoblastic Leukemia, Pediatric Acute Lymphoblastic Leukemia, in Relapse Acute Lymphoblastic Leukemia Recurrent Collapse <<	Phase 1 Phase 2	Recruiting	March 17, 2021	United Kingdom ... more >> Birmingham Children's Hospital Recruiting Birmingham, United Kingdom Principal Investigator: Alice Norton          Alder Hey Children's Hospital Recruiting Liverpool, United Kingdom Principal Investigator: Mark Caswell          Department of Paediatric Oncology, Royal Marsden Hospital, Sutton Recruiting London Borough of Sutton, United Kingdom Principal Investigator: Donna Lancaster          Haemato-Oncology Adult Unit, Royal Marsden Hospital, Sutton Recruiting London Borough of Sutton, United Kingdom Sub-Investigator: David Taussig          University College Hospital Recruiting London, United Kingdom Principal Investigator: Adele Fielding          The Christie Hospital Recruiting Manchester, United Kingdom Principal Investigator: Anna Castleton          Freeman Hospital Recruiting Newcastle, United Kingdom Sub-Investigator: Tobias Menne          Great North Children's Hospital, Royal Victoria Infirmary Recruiting Newcastle, United Kingdom Principal Investigator: Geoff Shenton Collapse <<

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• 参考文献

• [1] Janice M Huss,et al. Constitutive activities of estrogen-related receptors: Transcriptional regulation of metabolism by the ERR pathways in health and disease. Biochim Biophys Acta. 2015 Sep;1852(9):1912-27.

  [2] Krista McFarland,et al. AC-186, a selective nonsteroidal estrogen receptor β agonist, shows gender specific neuroprotection in a Parkinson's disease rat model. ACS Chem Neurosci. 2013 Sep 18;4(9):1249-55.

  [3] Jian-Nong Ma,et al. Estrogen Receptor Beta Selective Agonists as Agents to Treat Chemotherapeutic-Induced Neuropathic Pain. ACS Chem Neurosci. 2016 Sep 21;7(9):1180-7.

  [4] Sonia George,et al. Nonsteroidal selective androgen receptor modulators and selective estrogen receptor β agonists moderate cognitive deficits and amyloid-β levels in a mouse model of Alzheimer's disease. ACS Chem Neurosci. 2013 Dec 18;4(12):1537-48.