Abstract
Dose-limiting toxicity to healthy tissues is among the major hurdles in anticancer treatment along with intrinsic or acquired multi-drug resistance. Development of small molecule inhibitors (SMI) specific for antiapoptotic Bcl-2 proteins is a novel approach in a way that these antagonists are aimed to interfere with specific protein-protein interactions unlike conventional chemo-/radiotherapies. SMIs of antiapoptotic Bcl-2 proteins are assumed to compete with proapoptotic Bcl-2s to occupy BH3 docking grooves on the surfaces of antiapoptotic family members. Instead of directly initiating cell death, these inhibitors are intended to decrease apoptotic threshold in tumor cells that were already primed to death. In this regard, antiapoptotic Bcl-2 protein SMIs have the advantage of lower normal tissue toxicity relative to conventional anticancer therapies that interfere with general mechanisms including DNA synthesis, mitosis and tyrosine kinase activity. Besides, Bcl-2 antagonists were shown to potentiate efficacies of established drugs in several hematological malignancies and solid tumors which render them promising candidates for combination anticancer therapy. Utilizing these SMIs in such a way may prove to decrease the patient drug load by diminishing the required chemo-/radiotherapy dose. This review summarizes and compares BH3 mimetics on the basis of specificity, mode of action and efficacy, as well as providing remarks on their therapeutical potential and routes of development in near future.
Keywords: ABT-737, anticancer, apoptosis, Bcl-2, BH3 mimetic, cancer, gossypol, small molecule inhibitor, obatoclax
Current Medicinal Chemistry
Title:Bcl-2 Inhibitors: Emerging Drugs in Cancer Therapy
Volume: 19 Issue: 12
Author(s): C. Bodur and H. Basaga
Affiliation:
Keywords: ABT-737, anticancer, apoptosis, Bcl-2, BH3 mimetic, cancer, gossypol, small molecule inhibitor, obatoclax
Abstract: Dose-limiting toxicity to healthy tissues is among the major hurdles in anticancer treatment along with intrinsic or acquired multi-drug resistance. Development of small molecule inhibitors (SMI) specific for antiapoptotic Bcl-2 proteins is a novel approach in a way that these antagonists are aimed to interfere with specific protein-protein interactions unlike conventional chemo-/radiotherapies. SMIs of antiapoptotic Bcl-2 proteins are assumed to compete with proapoptotic Bcl-2s to occupy BH3 docking grooves on the surfaces of antiapoptotic family members. Instead of directly initiating cell death, these inhibitors are intended to decrease apoptotic threshold in tumor cells that were already primed to death. In this regard, antiapoptotic Bcl-2 protein SMIs have the advantage of lower normal tissue toxicity relative to conventional anticancer therapies that interfere with general mechanisms including DNA synthesis, mitosis and tyrosine kinase activity. Besides, Bcl-2 antagonists were shown to potentiate efficacies of established drugs in several hematological malignancies and solid tumors which render them promising candidates for combination anticancer therapy. Utilizing these SMIs in such a way may prove to decrease the patient drug load by diminishing the required chemo-/radiotherapy dose. This review summarizes and compares BH3 mimetics on the basis of specificity, mode of action and efficacy, as well as providing remarks on their therapeutical potential and routes of development in near future.
Export Options
About this article
Cite this article as:
Bodur C. and Basaga H., Bcl-2 Inhibitors: Emerging Drugs in Cancer Therapy, Current Medicinal Chemistry 2012; 19 (12) . https://dx.doi.org/10.2174/092986712800099839
DOI https://dx.doi.org/10.2174/092986712800099839 |
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
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
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
-
Role of miR-193a in Cancer: Complexity and Factors Control the Pattern of its Expression
Current Cancer Drug Targets Targeting Tumor Ubiquitin-Proteasome Pathway with Polyphenols for Chemosensitization
Anti-Cancer Agents in Medicinal Chemistry New Perspectives in the Pharmacological Treatment of Non-Melanoma Skin Cancer
Current Drug Targets Bioinformatic Analysis Reveals Key Genes and Pathways in Aging Brain of Senescence-accelerated Mouse P8 (SAMP8)
CNS & Neurological Disorders - Drug Targets Poxvirus Cancer Therapy
Recent Patents on Anti-Infective Drug Discovery Laminin-332-Integrin Interaction: A Target For Cancer Therapy?
Current Medicinal Chemistry Prognostic and Predictive Biomarkers in Cancer
Current Cancer Drug Targets Immune Checkpoint Inhibitors in the Treatment of Cancer
Current Reviews in Clinical and Experimental Pharmacology Recent Advances in Small Molecule Inhibitors of VEGFR and EGFR Signaling Pathways
Current Topics in Medicinal Chemistry A Storage Protein-Like Trypsin Inhibitor from the Moth Bean (Phaseolus acutifolius) with Antiproliferative Activity Toward Lymphoma Cells
Protein & Peptide Letters Lipid based Nanocapsules: A Multitude of Biomedical Applications
Current Pharmaceutical Biotechnology AAV as An Immunogen
Current Gene Therapy HIF Prolyl 4-Hydroxylases and their Potential as Drug Targets
Current Pharmaceutical Design Natural Compounds as Antagonists of Canonical Wnt/β-Catenin Signaling
Current Chemical Biology The Role of Carrier Geometry in Overcoming Biological Barriers to Drug Delivery
Current Pharmaceutical Design microRNAs-based Predictor Factor in Patients with Migraine-ischemic Stroke
MicroRNA Comparative Proteomics and Bioinformatics Analysis of Tissue from Non-Small Cell Lung Cancer Patients
Current Proteomics Prevention of Colitis-associated Cancer: Natural Compounds that Target the IL-6 Soluble Receptor
Anti-Cancer Agents in Medicinal Chemistry Metabolomics and the Diagnosis of Human Diseases -A Guide to the Markers and Pathophysiological Pathways Affected
Current Medicinal Chemistry TRAIL-Based Therapeutic Approaches for the Treatment of Pediatric Malignancies
Current Medicinal Chemistry