[6-30]Development of Cocaine Hydrolase for Cocaine Addiction Treatment.

报告题目:Development of Cocaine Hydrolase for Cocaine Addiction Treatment.

报 告 人:陈侠斌博士(美国肯塔基大学药学院博士后)




Cocaine abuse is a world-wide public health and social problem without a U.S. Food and Drug Administration (FDA)-approved medication. An ideal anti-cocaine medication would accelerate cocaine metabolism producing biologically inactive metabolites by administration of an efficient cocaine-specific exogenous enzyme. Recent studies have led to discovery of the desirable, highly efficient human cocaine hydrolases (hCocHs) that can efficiently detoxify and inactivate cocaine without affecting normal functions of central nervous system (CNS). Preclinical and clinical data have demonstrated that these hCocHs are safe for use in humans and effective for accelerating cocaine metabolism. However, the actual therapeutic use of a hCocH in cocaine addiction treatment is limited by the short biological half-life (e.g. 8 hours or shorter in rats) of the hCocH. In development of the long-acting hCocHs, we have designed and discovered a novel hCocH form, catalytic antibody analog, which is an Fc-fused hCocH dimer (hCocH-Fc). The hCocH-Fc has not only a high catalytic efficiency against cocaine, but also a considerably longer biological half-life. A single dose of hCocH-Fc was able to accelerate cocaine metabolism in rats even after 20 days and, thus, block cocaine-induced hyperactivity and cocaine self-administration for a long period of time. Currently this enzyme entity is under large-scale protein production in a CRO company.



Xiabin Chen (陈侠斌) is currently a Postdoc Scholar majoring in drug discovery and protein engineering at College of Pharmacy, University of Kentucky. During his tenure (Postdoc and PhD training) at University of Kentucky, he firstly demonstrated the metabolic enzymes of cocaine metabolite benzoylecgonine for cocaine overdose, and developed the first long-acting cocaine hydrolase for cocaine addiction. Due to his work in protein drug discovery, he was selected for the 2015 AAPS (American Association of Pharmaceutical Scientists) Graduate Student Research Award in Biotechnology, and the 2016 National Award for Outstanding Self-financed Chinese Students Studying Abroad. Before joining University of Kentucky, he received the Bachelar’s degree in Bioscience from Beijing Normal University, and Master’s degres in Medicine from Peking Union Medical College.