A new Chinese medicine, acoladine, may be a new therapy for drug-resistant prostate cancer

Carcinogenesis (if 5.266), an international well-known cancer journal, recently published an article entitled "a new treatment method for prostate cancer: akoladine activates aromatic hydrocarbon receptor to target androgen receptor and its variant isomer" The research was completed by Professor EU Leong Yong of School of medicine, National University of Singapore Prostate cancer is a hormone stimulated disease, which is a high incidence cancer in male patients Due to the large number of patients, prostate cancer drugs have been a hot area of drug research and development At present, androgen sensitive prostate cancer can be effectively controlled by drugs, but there is still a great clinical need for androgen insensitive prostate cancer patients The sustained activation of androgen receptor (AR) signaling pathway is an important factor in the development of androgen insensitive prostate cancer, in which the C-terminal deletion variant of AR (ARVs) plays a key role A series of drugs, such as enzalutamide and abiraterone, have been developed based on AR targets, but more than 30% of prostate cancer patients soon developed drug resistance Further research found that their drug resistance is highly related to ar-v7, the most important variant of ARVs However, there is no effective drug for ar-v7 in clinic, so the development of drug targeting ar-v7 has become a hot spot in international drug research and development Aromatic hydrocarbon receptor (AHR) is a cytoplasmic transcription factor, which plays an important role in the regulation of autoimmunity and tumor immunity Preclinical studies and tumor tissue studies showed that the combination of tryptophan (TRP) metabolite KYN and AHR would affect the selection of re differentiation of Na gave CD4 + Th cells, making them more likely to differentiate into Treg cell subsets than Th17 cell subsets capable of producing cytokine IL-17 Professor Yong's research team found for the first time that akoladine, a natural isopentene flavonoid, can target AR and ar-v7 Akoladine promotes ubiquitination degradation of AR and ar-v7 by combining with AHR In androgen sensitive and non sensitive prostate cancer mouse models, akoradine showed inhibitory effect on AR signaling pathway and tumor growth, and had no significant toxicity In this paper, it is suggested that akoladine may be a new drug molecule for the treatment of AR positive prostate cancer Akoladine is a national first-class original new drug of traditional Chinese medicine / natural medicine developed by Beijing Aoji pharmaceutical science and Technology Co., Ltd., which has full independent intellectual property rights and is supported by major new drug creation projects of the 12th Five Year Plan, as well as the capital injection of a number of venture capital companies (such as IDG, Junlian capital, Qiming capital, Lida capital, etc.) At present, the phase II clinical trial of akoradine is about to be completed, and the expected goal has been achieved Due to the breakthrough progress in the research of mechanism of action and biomarkers of the drug, the application for new drug certificate will be submitted to the State Food and Drug Administration in June 2015 with breakthrough therapy Attachment: Meng Kun, R & D team of akoladine, a new anti-tumor class 1 drug -- R & D team of targeted therapeutic drugs targeting cancer stem cells from small molecules to antibodies Meng Kun, male, Ph.D in biochemistry, State Key Laboratory of biomembrane and membrane bioengineering, Chinese Academy of Sciences, Ph.D in Harvard Medical School and Washington University School of medicine, St Louis, master of management (MPA) in Kennedy School, Harvard University, chairman and CEO of Beijing Aoji Pharmaceutical Technology Co., Ltd., director of Chinese Academy of traditional medicine, professional committee of Chinese patent medicine and AI Vice chairman of HIV prevention and control committee and executive director of China Association of pharmaceutical biotechnology He has successively served as the CEO of the Sino foreign joint venture traditional Chinese Medicine Technology Development Co., Ltd., executive director and technical director of Hong Kong natural pharmaceutical Holding Co., Ltd / Zhuhai Jianxin Pharmaceutical Co., Ltd He is mainly engaged in the research and development of new drugs of traditional Chinese medicine and natural medicine, undertakes a number of national major special projects, and presides over the research and application of "Chuankezhi Injection", a class II new drug of traditional Chinese medicine He has more than 20 new drug invention patents and published more than 30 academic papers In the world, we first found the functional receptor (rptp ζ) of multifunctional growth factor (PTN) and the substrate (β - Catenin) of the receptor, which was published in the Journal of the National Academy of Sciences of the United States, cited more than 270 times by international peers, and specially commented by the authoritative journals "Physics Review", "IUBMB life" and "nature", which is one of the major breakthroughs in this field in the past decade He won the nomination award of the first "top ten outstanding youth of Chinese medicine" and the first prize of science and technology of "Chinese society of Chinese medicine" Led the team to develop the world's first target anti-tumor class 1 new drug, akoladine, which has entered the clinical IIA stage Among the team members, 2 were selected into the municipal "overseas high-level talents" plan and 1 was selected into the national "thousand talents plan" The company has obtained financing of nearly 20 million US dollars from many venture capital institutions such as IDG capital About Beijing Aoji Pharmaceutical Technology Co., Ltd Beijing Aoji Pharmaceutical Technology Co., Ltd was formally established in Beijing, China in 2006 It is a high-tech enterprise with world leading and international cutting-edge technology, which is dominated by the research and development of new drugs The company has the only global patent for the new estrogen receptor ER alpha 36 drug target, and is committed to developing the world's first new anti-cancer drugs targeting cancer stem cells The R & D management team of the company has rich experience in R & D of new drugs at home and abroad, and many of its members have been selected into the "thousand talents plan", "Beijing overseas talents gathering project" and "Beijing hundred leading talents plan" The company supports long-term development strategy with world famous scientists as scientific consultants At the same time, the company has maintained close cooperation with key scientific research institutions and business partners at home and abroad, and has received strong support from many government funds, such as the "11th Five Year Plan" major new drug development, the "12th Five Year Plan" major new drug development, and the "innovation fund", which has attracted the investment of well-known venture capital companies for the research, development and industrialization of original anti-cancer drugs