Abstract
The antitumour enzyme L-asparaginase (L-asparagine amidohydrolase, EC 3.5.1.1, ASNase), which catalyses the deamidation of L-asparagine (Asn) to L-aspartic acid and ammonia, has been used for many years in the treatment of acute lymphoblastic leukaemia. Also NK tumours, subtypes of myeloid leukaemias and T-cell lymphomas respond to ASNase, and ovarian carcinomas and other solid tumours have been proposed as additional targets for ASNase, with a potential role for its glutaminase activity. The increasing attention devoted to the antitumour activity of ASNase prompted us to analyse recent patents specifically concerning this enzyme. Here, we first give an overview of metabolic pathways affected by Asn and Gln depletion and, hence, potential targets of ASNase. We then discuss recent published patents concerning ASNases. In particular, we pay attention to novel ASNases, such as the recently characterised ASNase produced by Helicobacter pylori, and those presenting amino acid substitutions aimed at improving enzymatic activity of the classical Escherichia coli enzyme. We detail modifications, such as natural glycosylation or synthetic conjugation with other molecules, for therapeutic purposes. Finally, we analyse patents concerning biotechnological protocols and strategies applied to production of ASNase as well as to its administration and delivery in organisms.
Keywords: Acute lymphoblastic leukaemia, amino acid metabolism, asparagine, cancer, glutaminase, glutamine, L-asparaginase, myeloid leukaemias, T-cell lymphomas, ovarian carcinomas
Recent Patents on Anti-Cancer Drug Discovery
Title: Expanding Targets for a Metabolic Therapy of Cancer: L-Asparaginase
Volume: 7 Issue: 1
Author(s): Daniele Covini, Saverio Tardito, Ovidio Bussolati, Laurent R. Chiarelli, Maria V. Pasquetto, Rita Digilio, Giovanna Valentini and Claudia Scotti
Affiliation:
Keywords: Acute lymphoblastic leukaemia, amino acid metabolism, asparagine, cancer, glutaminase, glutamine, L-asparaginase, myeloid leukaemias, T-cell lymphomas, ovarian carcinomas
Abstract: The antitumour enzyme L-asparaginase (L-asparagine amidohydrolase, EC 3.5.1.1, ASNase), which catalyses the deamidation of L-asparagine (Asn) to L-aspartic acid and ammonia, has been used for many years in the treatment of acute lymphoblastic leukaemia. Also NK tumours, subtypes of myeloid leukaemias and T-cell lymphomas respond to ASNase, and ovarian carcinomas and other solid tumours have been proposed as additional targets for ASNase, with a potential role for its glutaminase activity. The increasing attention devoted to the antitumour activity of ASNase prompted us to analyse recent patents specifically concerning this enzyme. Here, we first give an overview of metabolic pathways affected by Asn and Gln depletion and, hence, potential targets of ASNase. We then discuss recent published patents concerning ASNases. In particular, we pay attention to novel ASNases, such as the recently characterised ASNase produced by Helicobacter pylori, and those presenting amino acid substitutions aimed at improving enzymatic activity of the classical Escherichia coli enzyme. We detail modifications, such as natural glycosylation or synthetic conjugation with other molecules, for therapeutic purposes. Finally, we analyse patents concerning biotechnological protocols and strategies applied to production of ASNase as well as to its administration and delivery in organisms.
Export Options
About this article
Cite this article as:
Covini Daniele, Tardito Saverio, Bussolati Ovidio, R. Chiarelli Laurent, V. Pasquetto Maria, Digilio Rita, Valentini Giovanna and Scotti Claudia, Expanding Targets for a Metabolic Therapy of Cancer: L-Asparaginase, Recent Patents on Anti-Cancer Drug Discovery 2012; 7 (1) . https://dx.doi.org/10.2174/157489212798358001
DOI https://dx.doi.org/10.2174/157489212798358001 |
Print ISSN 1574-8928 |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-3970 |
Call for Papers in Thematic Issues
Novel anti-cancer drugs in photoimmunotherapy management: from bench to translational research
In recent years, traditional cancer treatments, such as surgery, chemotherapy, and radiation treatment, etc., may damage the pathological tissue and normal cells. The ideal tumor treatment should be noninvasive, eliminating the primary tumor, making the body produce systemic tumor-specific immunity, eliminating metastases, and having less /no side effects. Recent Patents ...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
Related Articles
-
Structure-Function Relationships and Clinical Applications of L-Asparaginases
Current Medicinal Chemistry Novel and Emerging Drugs for Acute Myeloid Leukemia: Pharmacology and Therapeutic Activity
Current Medicinal Chemistry Perspectives in Biomolecular Therapeutic Intervention in Cancer: From the Early to the New Strategies With Type I Interferons
Current Medicinal Chemistry Chemoprevention of Colorectal Cancer: Ready for Routine Use?
Current Topics in Medicinal Chemistry Patents in Cancer Stem Cells
Recent Patents on Biomarkers Emerging Breast Cancer Biomarkers
Current Cancer Therapy Reviews Signaling Pathways Modulating Dependence of Lung Cancer on Mutant Epidermal Growth Factor Receptor and Mechanisms of Intrinsic and Acquired Resistance to Tyrosine Kinase Inhibitors
Current Pharmaceutical Design Targeting Cancer Stem Cells with Repurposed Drugs to Improve Current Therapies
Recent Patents on Anti-Cancer Drug Discovery Cancer Stem Cells Switch on Tumor Neovascularization
Current Molecular Medicine Immune Function in Pregnant Women with Affective Disorders
Current Psychiatry Reviews Advances in Translational Pharmacological Investigations in Identifying and Validating Molecular Targets of Natural Product Anticancer Agents
Current Cancer Drug Targets New and Highly Potent Antitumor Natural Products from Marine-Derived Fungi: Covering the Period from 2003 to 2012
Current Topics in Medicinal Chemistry Advances on Semisynthesis, Total Synthesis, and Structure-Activity Relationships of Honokiol and Magnolol Derivatives
Mini-Reviews in Medicinal Chemistry Targeting Heat Shock Proteins 70/90 and Proteasome for Cancer Therapy
Current Medicinal Chemistry Dual Topoisomerase I / II Inhibitors in Cancer Therapy
Current Topics in Medicinal Chemistry Design, Synthesis and Antiproliferative Activity of 2-Acetamidothiazole-5- carboxamide Derivatives
Medicinal Chemistry Regulation of MET Receptor Signaling by SOCS1 and its Implications for Hepatocellular Carcinoma
Current Pharmaceutical Design The Genetic Landscapes of Inflammation-Driven Gastrointestinal Tract Cancers
Current Pharmaceutical Design Lipid-Based Drug Delivery Systems for Cancer Treatment
Current Drug Targets Cancer Stem Cells in Solid and Liquid Tissues of Breast Cancer Patients: Characterization and Therapeutic Perspectives
Current Cancer Drug Targets