{"doi":"10.1038/s41598-024-61646-7","title":"In vitro and in vivo stability of a highly efficient long-acting cocaine hydrolase","abstract":"It is recognized as a promising therapeutic strategy for cocaine use disorder to develop an efficient enzyme which can rapidly convert cocaine to physiologically inactive metabolites. We have designed and discovered a series of highly efficient cocaine hydrolases, including CocH5-Fc(M6) which is the currently known as the most efficient cocaine hydrolase with both the highest catalytic activity against (-)-cocaine and the longest biological half-life in rats. In the present study, we characterized the time courses of protein appearance, pH, structural integrity, and catalytic activity against cocaine in vitro and in vivo of a CocH5-Fc(M6) bulk drug substance produced in a bioreactor for its in vitro and in vivo stability after long-time storage under various temperatures (- 80, - 20, 4, 25, or 37 °C). Specifically, all the tested properties of the CocH5-Fc(M6) protein did not significantly change after the protein was stored at any of four temperatures including - 80, - 20, 4, and 25 °C for ~ 18 months. In comparison, at 37 °C, the protein was less stable, with a half-life of ~ 82 days for cocaine hydrolysis activity. Additionally, the in vivo studies further confirmed the linear elimination PK profile of CocH5-Fc(M6) with an elimination half-life of ~ 9 days. All the in vitro and in vivo data on the efficacy and stability of CocH5-Fc(M6) have consistently demonstrated that CocH5-Fc(M6) has the desired in vitro and in vivo stability as a promising therapeutic candidate for treatment of cocaine use disorder.","journal":"Scientific Reports","year":2024,"id":475735,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9508,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":414817,"name":"Huimei Wei","orcid":null,"position":1,"is_corresponding":false},{"id":413497,"name":"Jing Deng","orcid":"0000-0003-3754-7643","position":2,"is_corresponding":false},{"id":1145733,"name":"Madeline J. Stewart","orcid":null,"position":3,"is_corresponding":false},{"id":1313034,"name":"Johnathan E LeSaint","orcid":null,"position":4,"is_corresponding":false},{"id":1145734,"name":"Annet Kyomuhangi","orcid":null,"position":5,"is_corresponding":false},{"id":1108632,"name":"Shawn Park","orcid":null,"position":6,"is_corresponding":false},{"id":1313035,"name":"Elise C. Maul","orcid":null,"position":7,"is_corresponding":false},{"id":413499,"name":"Chang‐Guo Zhan","orcid":"0000-0002-4128-7269","position":8,"is_corresponding":false},{"id":413498,"name":"Fang Zheng","orcid":"0000-0002-5699-8063","position":9,"is_corresponding":false},{"id":440657,"name":"Linyue Shang","orcid":null,"position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":null,"created_at":"2026-07-19T02:06:21.071690Z","pmid":"38740850","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}