Title |
Development of Fc-Fused Cocaine Hydrolase for Cocaine Addiction Treatment: Catalytic and Pharmacokinetic Properties
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Published in |
The AAPS Journal, March 2018
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DOI | 10.1208/s12248-018-0214-9 |
Pubmed ID | |
Authors |
Xiabin Chen, Jing Deng, Wenpeng Cui, Shurong Hou, Jinling Zhang, Xirong Zheng, Xin Ding, Huimei Wei, Ziyuan Zhou, Kyungbo Kim, Chang-Guo Zhan, Fang Zheng |
Abstract |
Cocaine abuse is a worldwide public health and social problem without a US Food and Drug Administration (FDA)-approved medication. Accelerating cocaine metabolism that produces biologically inactive metabolites by administration of an efficient cocaine hydrolase (CocH) has been recognized as a promising strategy for cocaine abuse treatment. However, the therapeutic effects of CocH are limited by its short biological half-life (e.g., 8 h or shorter in rats). In this study, we designed and prepared a set of Fc-fusion proteins constructed by fusing Fc(M3) with CocH3 at the N-terminus of CocH3. A linker between the two protein domains was optimized to improve both the biological half-life and catalytic activity against cocaine. It has been concluded that Fc(M3)-G6S-CocH3 not only has fully retained the catalytic efficiency of CocH3 against cocaine but also has the longest biological half-life (e.g., ∼ 136 h in rats) among all of the long-acting CocHs identified so far. A single dose (0.2 mg/kg, IV) of Fc(M3)-G6S-CocH3 was able to significantly attenuate 15 mg/kg cocaine-induced hyperactivity for at least 11 days (268 h) after the Fc(M3)-G6S-CocH3 administration. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 2 | 67% |
Unknown | 1 | 33% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 3 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 9 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Bachelor | 2 | 22% |
Student > Ph. D. Student | 1 | 11% |
Student > Master | 1 | 11% |
Researcher | 1 | 11% |
Student > Postgraduate | 1 | 11% |
Other | 0 | 0% |
Unknown | 3 | 33% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 2 | 22% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 11% |
Agricultural and Biological Sciences | 1 | 11% |
Medicine and Dentistry | 1 | 11% |
Neuroscience | 1 | 11% |
Other | 0 | 0% |
Unknown | 3 | 33% |