Apoptosis: potential therapeutic targets for new drug discovery.
Apoptosis is involved in a wide range of pathologic conditions, including neurodegenerative, autoimmune diseases, cardiovascular diseases and cancer. Therefore, the ability to understand and manipulate the cell death machinery is an obvious goal of medical research. Novel therapeutic approaches to modulate disease by regulating apoptosis are being tested in preclinical and clinical settings. Approaches include the traditional use of small molecules to target specific players in the apoptosis cascade. As our understanding of apoptosis increases, further opportunities will arise for tailor-made therapies that will result in improved clinic. From variety of compounds are discovered in this field and only few are found in the preclinical and clinical trials. The lack of specific potent nonpeptide apoptosis inducers and/or inhibitors has limited for a long time the clinical investigation of this target. But in the last few years the renewed interest of pharmaceutical companies has been giving a strong impulse to the research in this area. This review considers the molecular mechanisms of apoptosis and their interaction in regulation of apoptosis. We also focus on recent developments of nonpeptide apoptosis modulators and their progress in drug lead discovery.
Jana
Snehasis
S
Metabolism and Pharmacokinetics Division, New Drug Discovery and Research, Ranbaxy Research Laboratories, Plot-20, Sector-18, Udyog Vihar, Industrial Area, Gurgaon, Haryana 122015, India.
Paliwal
Jyoti
J
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction; D013730:Terphenyl Compounds / Q000494:pharmacology; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism
D061945:Caspase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D013730:Terphenyl Compounds; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D020169:Caspases