Modulating apoptosis: current applications and prospects for future drug development.
Agents modulating apoptosis are of extraordinary promise for the treatment of several states of disease including cancer, AIDS, neurodegenerative and ischemic diseases. In this review a brief summary of cellular pathways relevant to programmed cell death first is given and potential therapeutic targets therein are emphasized. Current efforts in drug development are discussed from a mechanistic, biochemical point of view and pro- and anti-apoptotic strategies are related to the respective diseases. Therapeutic approaches addressed in this paper include the design and activity of novel low molecular weight agents (e.g. caspase inhibitors) as well as gene therapy (e.g. p53, adenovirus as vector in cancer treatment). In final sections, the latest findings in the field of apoptosis are highlighted and future applications are outlined.
Deigner
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HP
Institute of Pharmaceutical Chemistry and Institute of Anatomy and Cell Biology III, Im Neuenheimer Feld 364 and 307, Heidelberg, 69120, Germany. Hans-Peter.Deigner@urz.uni-heidelberg.de
Kinscherf
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D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002518:Ceramides / Q000502:physiology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D003574:Cytochrome c Group / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology; D018384:Oxidative Stress; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology; D019014:fas Receptor / Q000502:physiology
D002518:Ceramides; D015853:Cysteine Proteinase Inhibitors; D003574:Cytochrome c Group; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D018124:Receptors, Tumor Necrosis Factor; D019014:fas Receptor