Abstract
Several groups working in the field of the development of new antituberculosis drugs have recently reported active compounds targeting mycobacterial enzyme DprE1. Along with its counterpart, DprE2, it catalyses a unique epimerization reaction resulting in the synthesis of decaprenylphosphoryl arabinose, the single donor of arabinosyl residues for the build-up of arabinans, fundamental components of the mycobacterial cell wall. This review presents the historical background leading to the discovery of DprE1, focusing on the biochemical and structural characterization of this important emerging target and introducing the molecules acting on DprE1 including the development of the most successful series – the benzothiazinones, currently in late pre-clinical development, which turned to be suicide inhibitors of DprE1.
Keywords: Tuberculosis, drug target, DprE1, structure, inhibitors, SAR, benzothiazinones.
Current Pharmaceutical Design
Title:DprE1 - from the Discovery to the Promising Tuberculosis Drug Target
Volume: 20 Issue: 27
Author(s): Katarina Mikusova, Vadim Makarov and Joao Neres
Affiliation:
Keywords: Tuberculosis, drug target, DprE1, structure, inhibitors, SAR, benzothiazinones.
Abstract: Several groups working in the field of the development of new antituberculosis drugs have recently reported active compounds targeting mycobacterial enzyme DprE1. Along with its counterpart, DprE2, it catalyses a unique epimerization reaction resulting in the synthesis of decaprenylphosphoryl arabinose, the single donor of arabinosyl residues for the build-up of arabinans, fundamental components of the mycobacterial cell wall. This review presents the historical background leading to the discovery of DprE1, focusing on the biochemical and structural characterization of this important emerging target and introducing the molecules acting on DprE1 including the development of the most successful series – the benzothiazinones, currently in late pre-clinical development, which turned to be suicide inhibitors of DprE1.
Export Options
About this article
Cite this article as:
Mikusova Katarina, Makarov Vadim and Neres Joao, DprE1 - from the Discovery to the Promising Tuberculosis Drug Target, Current Pharmaceutical Design 2014; 20 (27) . https://dx.doi.org/10.2174/138161282027140630122724
DOI https://dx.doi.org/10.2174/138161282027140630122724 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
Innovative Formulations for the Controlled and Site-specific Delivery of Antiinflammatory Drugs
Current Pharmaceutical Design A Remarkably Faster Approach Towards 1,2,3-Triazolyl Quinolines Via CuAAC in Water: Their Crystal Structure Analysis and Antibacterial Activities
Letters in Drug Design & Discovery Mouse Models of Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Current Pharmaceutical Design Meet Our Editorial Board Member:
Current Organic Chemistry Fighting Diabetes: Lessons from Xenotransplantation and Nanomedicine
Current Pharmaceutical Design Lipid-based Nanocarriers Loaded with Taxanes for the Management of Breast Cancer: Promises and Challenges
Current Drug Targets Review of the Syntheses and Activities of Some Sulfur-Containing Drugs
Current Organic Synthesis Predicting Subcellular Localization of Mycobacterial Proteins by Using Chous Pseudo Amino Acid Composition
Protein & Peptide Letters Detection of the Incidence of Infections and Acute Biochemical Changes in Diffused Large B-Cell Lymphoma Patients Treated with Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (CHOP) with and without Rituximab
Current Drug Safety A Bibliometric Analysis of Global Research on Lophomonas Spp. in Scopus (1933-2019)
Infectious Disorders - Drug Targets Patent Selections:
Recent Patents on Anti-Infective Drug Discovery Carbonic Anhydrase Inhibition/Activation: Trip of a Scientist Around the World in the Search of Novel Chemotypes and Drug Targets
Current Pharmaceutical Design Scorpion Extracts Inhibit Tumor Growth in Esophageal Cancer and Lung Adenocarcinoma
Current Signal Transduction Therapy Patenting of Nanopharmaceuticals in Drug Delivery: No Small Issue
Recent Patents on Drug Delivery & Formulation Challenges and Successes Using Nanomedicines for Aerosol Delivery to the Airways
Current Gene Therapy Reviving an Old HIV-1 Gene: The HIV-1 Antisense Protein
Current HIV Research α-Galactosylceramide: Potential Immunomodulatory Activity and Future Application [General Articles]
Current Medicinal Chemistry Computational Studies of Free Radical-Scavenging Properties of Phenolic Compounds
Current Topics in Medicinal Chemistry Essential Structural and Functional Features of Small Heat Shock Proteins in Molecular Chaperoning Process
Protein & Peptide Letters Saccharomyces cerevisiae β-Carbonic Anhydrase: Inhibition and Activation Studies
Current Pharmaceutical Design