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Targeting Bcl-2 Family of Proteins: An Important Strategy in Cancer Therapeutics

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BCL-2 protein controls the intrinsic pathway of apoptosis and plays a crucial role in governing apoptotic cell death. It regulates mitochondrial outer membrane permeability, leading to the initiation of Caspase cascade. Till date there are 25 genes known to be the members of BCL-2 family. Some of them are pro-apoptotic and some are anti-apoptotic. Over expression of anti-apoptotic BCL-2 proteins has been observed in 80% of beta cell lymphomas and 90% of colorectal adenocarcinomas. Hence, BCL-2 proteins are valuable targets in designing anti-cancer agents. Peptides, Peptidomimetics and non-peptide antagonists are designed to trigger apoptosis by BCL-2 pathway. These drugs have exhibited promising results at pre-clinical and clinical levels. It is well known that apoptosis is also related to inflammatory responses; it will be interesting to explore the area of BCL-2 to design some drugs having anti-inflammatory action. This review gives an account of development of BCL-2 family of proteins as potential target in the varieties of diseases including special focus on cancer.

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Keywords: Anti-sense Agent (Oblimersen Sodium); Apogossypolone; Apoptosis; Autoimmunity; BCL-2; Cancer; Docetaxel; Extrinsic; Gossypol Derivatives; Hodgkins disease, leukemia; INHIBITORS; Intrinsic pathways; Lead optimization; Molecule Antagonist; Peptides; Peptidomimetics; Proteins; Synergy with agents; T lymphoid cells; Terphenyl derivatives; Therapeutics; abnormal growth; acute lymphoblastic leukemia; analogues; anti apoptotic; anticancer drug discovery; antiproliferative; benzoyl urea frame work; binding affinity; breast; breast cancers; cancer; carcinomas; caspase; cell death; cell division; cell lymphoma; cell shrinkage, membrane blebbing; chemotherapy; chromatin condensation; chromosomes; chronic lymphocytic leukemia; colorectal adenocarcinomas; cytotoxic agents; dendrite cells; embryogenesis; enantiomer; gene translocation; genetic information; gossypol; growth; homeostasis; mRNA; melanoma; micromolar affinity; migration of cells; mitochondrial membrane; mitochondrial outer membrane permeabilization (MOMP); multiple myeloma; mutations to DNA; myeloid lymphoma; neuronal cells; non-vital cell; oligonucleotide drug; oncogenic signal; patent protection; peripheral tolerance; pharmaceuticals; pharmacokinetic; pro-apoptotic; proliferation; prostate; proteolytic enzymes; purpurogallin; racemate; radiotherapy; screening combinatorial; self-antigen; sperms cells; thrombocytopenia; tumor; uclear fragmentation

Document Type: Research Article

Publication date: January 1, 2011

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  • Current Chemical Biology aims to publish full-length and mini reviews on exciting new developments at the chemistry-biology interface, covering topics relating to Chemical Synthesis, Science at Chemistry-Biology Interface and Chemical Mechanisms of Biological Systems.

    Current Chemical Biology covers the following areas: Chemical Synthesis (Syntheses of biologically important macromolecules including proteins, polypeptides, oligonucleotides, oligosaccharides etc.; Asymmetric synthesis; Combinatorial synthesis; Diversity-oriented synthesis; Template-directed synthesis; Biomimetic synthesis; Solid phase biomolecular synthesis; Synthesis of small biomolecules: amino acids, peptides, lipids, carbohydrates and nucleosides; and Natural product synthesis).

    Science at Chemistry-Biology Interface (Chemical informatics; Macromolecular catalysts and receptors; Enzymatic synthesis; Biosynthetic engineering; Combinatorial biosynthesis; Plant cell based chemistry; Bacterial and viral cell based chemistry; Chemistry of cellular processes in plants/animals; Receptor chemistry; Cell signaling chemistry; Drug design through understanding of disease processes; Synthetic biology; New high throughput screening techniques; Small molecular array fabrication; Chemical genomics; Chemical and biological approaches to carbohydrates proteins and nucleic acids design; Chemical and biological regulation of biosynthetic pathways; and Unnatural biomolecular analogs).
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