[HTML][HTML] Enzyme therapy: current challenges and future perspectives

M de la Fuente, L Lombardero… - International Journal of …, 2021 - mdpi.com
In recent years, enzymes have risen as promising therapeutic tools for different pathologies,
from metabolic deficiencies, such as fibrosis conditions, ocular pathologies or joint …

Development of a highly efficient long-acting cocaine hydrolase entity to accelerate cocaine metabolism

F Zheng, Z Jin, J Deng, X Chen, X Zheng… - Bioconjugate …, 2022 - ACS Publications
It is particularly challenging to develop a truly effective pharmacotherapy for cocaine use
disorder (CUD) treatment. Accelerating cocaine metabolism via hydrolysis at cocaine …

[HTML][HTML] Catalytic activities of a highly efficient cocaine hydrolase for hydrolysis of biologically active cocaine metabolites norcocaine and benzoylecgonine

L Shang, Z Jin, H Wei, S Park, CG Zhan, F Zheng - Scientific Reports, 2023 - nature.com
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 …

Cocaine hydrolase blocks cocaine‐induced dopamine transporter trafficking to the plasma membrane

J Deng, K Kim, X Zheng, L Shang, CG Zhan… - Addiction …, 2022 - Wiley Online Library
Cocaine blocks dopamine uptake via dopamine transporter (DAT) on plasma membrane of
neuron cells and, as a result, produces the high and induces DAT trafficking to plasma …

In vivo characterization of toxicity of norcocaethylene and norcocaine identified as the most toxic cocaine metabolites in male mice

X Zheng, L Shang, CG Zhan, F Zheng - Drug and alcohol dependence, 2019 - Elsevier
Background Majority of cocaine users also consume alcohol, and concurrent use of cocaine
and alcohol produces cocaethylene, norcocaine, norcocaethylene, and other non-toxic …

Clinical potential of a rationally engineered enzyme for treatment of cocaine dependence: Long-lasting blocking of the psychostimulant, discriminative stimulus, and …

T Zhang, H Wei, J Deng, F Zheng, CG Zhan - Neuropharmacology, 2020 - Elsevier
It is a grand challenge to develop a truly effective treatment of substance use disorder
(SUD), particularly for cocaine and other drugs without an FDA-approved treatment …

[HTML][HTML] In vitro and in vivo stability of a highly efficient long-acting cocaine hydrolase

L Shang, H Wei, J Deng, MJ Stewart, JE LeSaint… - Scientific Reports, 2024 - nature.com
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 …

Kinetic characterization of an efficient cocaine hydrolase against toxic metabolites of cocaine

M Zhan, S Hou, L Shang, X Chen, CG Zhan… - Organic & Biomolecular …, 2023 - pubs.rsc.org
In the presence of alcohol, cocaine metabolism produces a number of metabolites, including
three toxic ones (cocaethylene, norcocaine, and norcocaethylene) which are all more toxic …

Catalytic reaction mechanism for drug metabolism in human carboxylesterase-1: cocaine hydrolysis pathway

J Yao, X Chen, F Zheng, CG Zhan - Molecular pharmaceutics, 2018 - ACS Publications
Carboxylesterase-1 (CE-1) is a crucial enzyme responsible for metabolism/activation/
inactivation of xenobiotics (therapeutic agents, prodrugs, abused drugs, and …

Structure-based design and discovery of a long-acting cocaine hydrolase mutant with improved binding affinity to neonatal Fc receptor for treatment of cocaine abuse

F Zheng, X Chen, K Kim, T Zhang, H Huang, S Zhou… - The AAPS journal, 2020 - Springer
Despite decades of efforts to develop a pharmacotherapy for cocaine abuse treatment, there
is still no FDA-approved treatment of diseases associated with this commonly abused drug …