Drug development of oral GnRH receptor antagonist

Shijiazhuang Yiling Pharmaceutical Co., Ltd. has always adhered to the innovative development strategy of technology leading and market leading, and established a five in one operation model of "theory clinical research industry teaching". It has undertaken more than 60 national, provincial and ministerial level projects such as National 973, National 863, National Natural Science Foundation of China, and National Key R&D Plan. The company has developed more than 10 patented new drugs, including Tongxinluo capsule, Shensong Yangxin capsule, Qili Qiangxin capsule, Lianhua Qingwen, Bazi Bushen capsule, and won more than 800 patents and six national awards, including the first prize of national scientific and technological progress and the second prize of national scientific and technological progress. Five production and research and development bases have been established in Hebei and Beijing, and more than 30 traditional Chinese medicine raw material bases have been established nationwide. The production workshops have passed international certifications in multiple countries and regions such as the United States, the European Union, Canada, and New Zealand, establishing a comprehensive quality control system that meets international standards. Lianhua Qingwen has been launched in over 30 countries. The company is one of the top 10 Chinese herbal medicine enterprises, one of the top 20 listed pharmaceutical companies in China, one of the top 500 listed companies in China with market value, and one of the top 100 Chinese brand value enterprises.
Project introduction: 
Prostate cancer is one of the common malignant tumors in men. It is estimated that there will be 174650 new cases of prostate cancer in the United States in 2019, accounting for about 20% of the male patients with new cancer in the United States that year, and the incidence rate from 2011 to 2016 will be 109.2/100000. The incidence rate of prostate cancer in China is lower than that in western countries, but it has shown a significant upward trend in the past 10 years. In 2015, there were about 72000 new cases of prostate cancer in China, and the incidence rate increased from 5.62/100000 in 2000 to 10.23/100000 in 2015. 
Androgen deprivation therapy is one of the most important basic treatments for prostate cancer. Its main goal is to reduce serum testosterone and maintain it below the castration level. Common drugs include Gonadotropin-releasing hormone (GnRH) agonists and GnRH antagonists, among which GnRH antagonists are considered as the first choice for ADT treatment. GnRH receptor antagonists that
have been approved for marketing at present, such as Sittrarek and Garnerrek, are peptides, which require subcutaneous injection or intranasal spray, or injection of long-term storage, and cannot be Oral administration. The shortcomings of stimulating histamine release reaction at the injection site and slow clearance after stopping the administration limit their application. While non peptide GnRH receptor antagonists can be Oral administration to increase patient compliance, they also have low oral bioavailability and rapid metabolic clearance, resulting in higher clinical therapeutic dose and higher risk of hepatotoxicity. 
Therefore, in view of the existing problems of GnRH receptor antagonists, Yiling Pharmaceutical intends to develop an oral small molecule GnRH receptor antagonist with novel structure, high bioavailability and low toxicity to provide more effective and safe treatment options for patients with prostate cancer and Endometriosis. 
Countries of
interest
: Unlimited main problems to be solved through the project: In view of the problems of Elagolix, such as only medium and low cell permeability and low oral bioavailability, Yiling intends to carry out structure based Drug design, improve and optimize the structure of Elagolix, and screen new oral small molecule GnRH receptor antagonists with similar or better activity, safety, permeability, metabolic stability, and Druglikeness properties.