Evidence map›Paper›PMID 38740850›Full record

ArticleScientific reports2024

In vitro and in vivo stability of a highly efficient long-acting cocaine hydrolase.

Linyue Shang, Huimei Wei, Jing Deng, Madeline J Stewart, Johnathan E LeSaint, Annet Kyomuhangi, Shawn Park, Elise C Maul, Chang-Guo Zhan, Fang Zheng

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Linyue Shang *Molecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY, 40536, USA.
Huimei Wei *Molecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY, 40536, USA.
Jing Deng *Molecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY, 40536, USA.
Madeline J StewartMolecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY, 40536, USA.
Johnathan E LeSaintMolecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY, 40536, USA.
Annet KyomuhangiMolecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY, 40536, USA.
Shawn ParkMolecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY, 40536, USA.
Elise C MaulMolecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY, 40536, USA.
Chang-Guo ZhanMolecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY, 40536, USA. zhan@uky.edu.
Fang ZhengMolecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY, 40536, USA. fzhen2@uky.edu.

Funding

Development of a Long-acting Enzyme Therapy for Treatment of Cocaine AbuseU01DA051079 · NIDA · UNIVERSITY OF KENTUCKY · PI ZHAN, CHANG-GUO · 2020 to 2022
$11.8M
Development of Long-acting Cocaine Hydrolase as a Treatment for Cocaine AbuseUH3DA041115 · NIDA · UNIVERSITY OF KENTUCKY · PI ZHAN, CHANG-GUO · 2017 to 2019
$3.8M
Long-lasting cocaine-metabolizing enzyme for cocaine addiction treatmentR01DA035552 · NIDA · UNIVERSITY OF KENTUCKY · PI ZHAN, CHANG-GUO · 2013 to 2015
$3.4M
Redesign of Butyrylcholinesterase for Cocaine MetabolismR01DA013930 · NIDA · UNIVERSITY OF KENTUCKY · PI ZHAN, CHANG-GUO · 2003 to 2010
$2.4M
Ghrelin Deacylase as a Treatment for Opioid Polysubstance AbuseR01DA056646 · NIDA · UNIVERSITY OF KENTUCKY · PI ZHAN, CHANG-GUO, ZHENG, FANG · 2022 to 2025
$2.2M
Development of Long-acting Cocaine Hydrolase as a Treatment for Cocaine AbuseUH2DA041115 · NIDA · UNIVERSITY OF KENTUCKY · PI ZHAN, CHANG-GUO · 2015 to 2016
$2.2M
Development of a Cocaine-Metabolizing Enzyme for Drug Overdose TreatmentR01DA032910 · NIDA · UNIVERSITY OF KENTUCKY · PI ZHAN, CHANG-GUO · 2012 to 2015
$1.8M
Long-acting aldicarb hydrolase as a medical countermeasure for aldicarb poisoningUG3NS134920 · NINDS · UNIVERSITY OF KENTUCKY · PI ZHAN, CHANG-GUO, ZHENG, FANG · 2023 to 2024
$1.1M
Validation of ghrelin hydrolysis as an effective approach to treatment of substance use disordersU18DA052319 · NIDA · UNIVERSITY OF KENTUCKY · PI ZHENG, FANG · 2020 to 2020
$230k
NIDA NIH HHS R01 DA013930NIDA NIH HHS R01 DA032910NIDA NIH HHS R01 DA035552NIDA NIH HHS R01 DA056646NIDA NIH HHS U01 DA051079NIDA NIH HHS U18 DA052319NIDA NIH HHS UH2 DA041115NIDA NIH HHS UH3 DA041115NIH HHS U01 DA051079, UH2/UH3 DA041115, R01 DA056646, UG3/UH3 NS134920, U18 DA052319, R01 DA035552, R01 DA032910, and R01 DA013930NINDS NIH HHS UG3 NS134920
6 · The paper itself

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.

Indexed as

CocaineEnzyme StabilityAmidohydrolasesAnimalsCarboxylic Ester HydrolasesHalf-LifeHydrogen-Ion ConcentrationHydrolysisMaleRatsRecombinant ProteinsTemperatureAmidohydrolasesCarboxylic Ester HydrolasesCocainecocaine hydrolaseRecombinant ProteinsCocaine abuseCocaine hydrolaseEnzyme therapyPharmacokineticsProtein stability

Identifiers

PMID38740850
PMCPMC11091111

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.