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• W4315702437 abstract "Cocaine is a widely abused, hepatotoxic drug without an FDA-approved pharmacotherapy specific for cocaine addiction or overdose. It is recognized as a promising therapeutic strategy to accelerate cocaine metabolism which can convert cocaine to pharmacologically inactive metabolite(s) using an efficient cocaine-metabolizing enzyme. Our previous studies have successfully designed and discovered a highly efficient cocaine hydrolase, denoted as CocH5-Fc(M6), capable of rapidly hydrolyzing cocaine at the benzoyl ester moiety. In the present study, we determined the kinetic parameters of CocH5-Fc(M6) against norcocaine (kcat = 9,210 min-1, KM = 20.9 μM, and kcat/KM = 1.87 × 105 min-1 M-1) and benzoylecgonine (kcat = 158 min-1, KM = 286 μM, and kcat/KM = 5.5 × 105 min-1 M-1) for the first time. Further in vivo studies have demonstrated that CocH5-Fc(M6) can effectively accelerate clearance of not only cocaine, but also norcocaine (known as a cocaine metabolite which is more toxic than cocaine itself) and benzoylecgonine (known as an unfavorable long-lasting metabolite with some long-term toxicity concerns) in rats. Due to the desired high catalytic activity against norcocaine, CocH5-Fc(M6) is capable of quickly detoxifying both cocaine and its more toxic metabolite norcocaine after intraperitoneally administering lethal dose of 60 or 180 mg/kg cocaine. In addition, the ability of CocH5-Fc(M6) to accelerate clearance of benzoylecgonine should also be valuable for the use of CocH5-Fc(M6) in treatment of cocaine use disorder." @default.
• W4315702437 created "2023-01-12" @default.
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• W4315702437 date "2023-01-12" @default.
• W4315702437 modified "2023-09-23" @default.
• W4315702437 title "Catalytic activities of a highly efficient cocaine hydrolase for hydrolysis of biologically active cocaine metabolites norcocaine and benzoylecgonine" @default.
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• W4315702437 doi "https://doi.org/10.1038/s41598-022-27280-x" @default.
• W4315702437 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36635293" @default.
• W4315702437 hasPublicationYear "2023" @default.
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