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
-
In Silico and In Vitro Analysis of a Multiepitope L1-E7 Fusion Construct for Vaccine Development Against Human Papillomaviruses
Letters in Drug Design & Discovery How Immune-inflammatory Processes Link CNS and Psychiatric Disorders: Classification and Treatment Implications
CNS & Neurological Disorders - Drug Targets Minimally Invasive Approach to Endometrial Cancer: Robotics and Laparoscopy
Current Women`s Health Reviews Natural Compounds as Antagonists of Canonical Wnt/β-Catenin Signaling
Current Chemical Biology Retinoids as Critical Modulators of Immune Functions: New Therapeutic Perspectives for Old Compounds
Endocrine, Metabolic & Immune Disorders - Drug Targets miR-21, An Oncogenic Target miRNA for Cancer Therapy: Molecular Mechanisms and Recent Advancements in Chemo and Radio-resistance
Current Gene Therapy Inflammation in Ischemic Stroke Subtypes
Current Pharmaceutical Design Streamlined In Vivo Selection and Screening of Human Prostate Carcinoma Avid Phage Particles for Development of Peptide Based In Vivo Tumor Imaging Agents
Combinatorial Chemistry & High Throughput Screening Sanguinarine: A Double-Edged Sword of Anticancer and Carcinogenesis and Its Future Application Prospect
Anti-Cancer Agents in Medicinal Chemistry Comprehensive Profiling of the Low Molecular Weight Proteins and Peptides in Weak Cation Exchange Beads Human Serum Retentate
Protein & Peptide Letters Revealing Insights into Natural Products Against mcr-1-Producing Bacteria
Current Drug Targets Management of Locally Advanced Cancer Cervix an Indian Perspective
Reviews on Recent Clinical Trials Structural Modification of Sylibin to Derivatives of Sylibin/Hydnocarpin D/Silandrin, and Evaluation of their Cytotoxicity against Cancer Cells
Current Topics in Medicinal Chemistry Design of New Improved Curcumin Derivatives to Multi-targets of Cancer and Inflammation
Current Drug Targets Breaking the DNA Damage Response via Serine/Threonine Kinase Inhibitors to Improve Cancer Treatment
Current Medicinal Chemistry Metal Complexes, their Cellular Targets and Potential for Cancer Therapy
Current Pharmaceutical Design Recombinant Human p53 Adenovirus Injection (rAd-p53) Combined with Chemotherapy for 4 Cases of High-grade Serous Ovarian Cancer
Current Gene Therapy Mannosylated Solid Lipid Nanocarriers of Chrysin to Target Gastric Cancer: Optimization and Cell Line Study
Current Drug Delivery Role of Infrared Spectroscopy and Imaging in Cancer Diagnosis
Current Medicinal Chemistry The Emerging Role of Vascular Endothelial Growth Factor (VEGF) in Vascular Homeostasis: Lessons from Recent Trials with Anti-VEGF Drugs
Current Vascular Pharmacology