Abstract
Mammalian carboxylesterases are key serine hydrolases that catalyze the hydrolysis of a wide variety of ester compounds in the corresponding carboxylic acids and alcohols. In human, two major carboxylesterases, CES1 and CES2, have been identified and well-studied over the past decade. CES1 inhibitors have potential applications in the treatment of hypertriglyceridaemia, obesity and type 2 diabetes, owing to that this enzyme plays prominent role in the metabolism of cholesteryl esters. CES2 plays crucial roles in the metabolic activation of many prodrugs including anticancer agents capecitabine and CPT-11. Co-administration with CES2 inhibitors may ameliorate CPT-11 associated lifethreatening diarrhea or improve the half-lives of CES2-substrate drugs. The important roles of carboxylesterases in both endogenous and xenobiotic metabolism arouse great interest in the discovery and development of potent and selective inhibitors against these enzymes. This review is focused on the application potentials and recent advances in the discovery and development of carboxylesterases inhibitors. The inhibitory capacities and inhibition mechanism of a variety of carboxylesterases inhibitors including synthetic, semi-synthetic and natural compounds are comprehensively summarized. Furthermore, the key structural features and structure-activity relationships (SARs) of different classes of CES1 and CES2 inhibitors are discussed. All information and knowledge summarized in this review will be very helpful for the medicinal chemists to design and develop more potent and highly selective carboxylesterases inhibitors for potential biomedical applications.
Keywords: Carboxylesterases, CES1, CES2, Inhibitors, Structure-activity relationships (SARs), hydrolases.
Current Medicinal Chemistry
Title:Carboxylesterase Inhibitors: An Update
Volume: 25 Issue: 14
Author(s): Li-Wei Zou, Qiang Jin, Dan-Dan Wang, Qing-Kai Qian, Da-Cheng Hao, Guang-Bo Ge*Ling Yang
Affiliation:
- Institute of Interdisciplinary Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203,China
Keywords: Carboxylesterases, CES1, CES2, Inhibitors, Structure-activity relationships (SARs), hydrolases.
Abstract: Mammalian carboxylesterases are key serine hydrolases that catalyze the hydrolysis of a wide variety of ester compounds in the corresponding carboxylic acids and alcohols. In human, two major carboxylesterases, CES1 and CES2, have been identified and well-studied over the past decade. CES1 inhibitors have potential applications in the treatment of hypertriglyceridaemia, obesity and type 2 diabetes, owing to that this enzyme plays prominent role in the metabolism of cholesteryl esters. CES2 plays crucial roles in the metabolic activation of many prodrugs including anticancer agents capecitabine and CPT-11. Co-administration with CES2 inhibitors may ameliorate CPT-11 associated lifethreatening diarrhea or improve the half-lives of CES2-substrate drugs. The important roles of carboxylesterases in both endogenous and xenobiotic metabolism arouse great interest in the discovery and development of potent and selective inhibitors against these enzymes. This review is focused on the application potentials and recent advances in the discovery and development of carboxylesterases inhibitors. The inhibitory capacities and inhibition mechanism of a variety of carboxylesterases inhibitors including synthetic, semi-synthetic and natural compounds are comprehensively summarized. Furthermore, the key structural features and structure-activity relationships (SARs) of different classes of CES1 and CES2 inhibitors are discussed. All information and knowledge summarized in this review will be very helpful for the medicinal chemists to design and develop more potent and highly selective carboxylesterases inhibitors for potential biomedical applications.
Export Options
About this article
Cite this article as:
Zou Li-Wei, Jin Qiang, Wang Dan-Dan , Qian Qing-Kai , Hao Da-Cheng , Ge Guang-Bo*, Yang Ling, Carboxylesterase Inhibitors: An Update, Current Medicinal Chemistry 2018; 25 (14) . https://dx.doi.org/10.2174/0929867325666171204155558
DOI https://dx.doi.org/10.2174/0929867325666171204155558 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Current Insights of Inhibitors of p38 Mitogen-Activated Protein Kinase in Inflammation
Medicinal Chemistry Toll Like Receptors Signaling Pathways as a Target for Therapeutic Interventions
Current Signal Transduction Therapy Evaluation of the Risk/Benefit Ratio of Old and New Anti-Inflammatory Drugs
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Antiviral Activity of Substituted Salicylanilides - A Review
Mini-Reviews in Medicinal Chemistry Pathobiology and Therapeutic Implications of Tumor Acidosis
Current Medicinal Chemistry Mild Synthesis of mono-, bis- and tris 1,2-Dihydrobenzo[4,5]imidazo[1,2- a]pyrimidine Derivatives Using Alkyl Disulfamic Acid Functionalized Magnetic Nanoparticles
Current Organic Chemistry Editorial (Thematic Issue: Chemistry Bordering Biology: Highlights from the XXXIV Biennial Meeting of the RSEQ)
Current Topics in Medicinal Chemistry The Current Status and Future Perspectives of Studies of Cannabinoid Receptor 1 Antagonists as Anti-Obesity Agents
Current Topics in Medicinal Chemistry Heterocyclic Dications as a New Class of Telomeric G-Quadruplex Targeting Agents
Current Pharmaceutical Design COVID-19 Mortality and the Cytokine Storm: An Added Value for APOE Genotyping
Coronaviruses Updating the Chemistry and Biology of Cannabinoid CB2 Receptor – Specific Inverse Agonists
Current Topics in Medicinal Chemistry Editorial [Hot Topic: Opportunities and Potential Challenges for the Treatment of Metabolic Syndrome (Guest Editors: Kak-Shan Shia and Yu-Sheng Chao)]
Current Topics in Medicinal Chemistry Evaluation of Novel 7-(hetero)aryl-substituted Pyrazolo[1, 5-a]pyrimidines as Phosphodiesterase-4 Inhibitors
Letters in Drug Design & Discovery Indole-3-ethylsulfamoylphenylacrylamides with Potent Anti-proliferative and Anti-angiogenic Activities
Anti-Cancer Agents in Medicinal Chemistry Recent Developments of Target Based Coumarin Derivatives as Potential Anticancer Agents
Mini-Reviews in Medicinal Chemistry In Silico Prediction Models for Blood-Brain Barrier Permeation
Current Medicinal Chemistry Multi-Target Metal-Based Anticancer Agents
Current Topics in Medicinal Chemistry Nitric Oxide: Cancer Target or Anticancer Agent?
Current Cancer Drug Targets Evidence of Protein Binding by a Nucleopeptide Based on a Thyminedecorated L-Diaminopropanoic Acid through CD and In Silico Studies
Current Medicinal Chemistry Progress on Kinesin Spindle Protein Inhibitors as Anti-Cancer Agents
Anti-Cancer Agents in Medicinal Chemistry