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Reverse Pharmacology and Systems Approaches for Drug Discovery and Development

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While biotechnological advances, genomics and high throughput screenings or combinatorial and asymmetric syntheses have opened new vistas in drug discovery, the industry is facing a serious innovation deficit. Critics suggest that “we have become high throughput in technology, yet have remained low throughput in thinking”. Post marketing failures of blockbuster drugs have become major concerns of industries, leading to a significant shift in favor of single to multi targeted drugs and affording greater respect to traditional knowledge. Typical reductionist approach of modern science is being revisited over the background of systems biology and holistic approaches of traditional practices. Scientifically validated and technologically standardized botanical products may be explored on a fast track using innovative approaches like reverse pharmacology and systems biology, which are based on traditional medicine knowledge. Traditional medicine constitutes an evolutionary process as communities and individuals continue to discover practices transforming techniques. Many modern drugs have origin in ethnopharmacology and traditional medicine. Traditions are dynamic and not static entities of unchanging knowledge. Discovering reliable ‘living tradition’ remains a major challenge in traditional medicine. In many parts ‘little traditions’ of indigenous systems of medicine are disappearing, yet their role in bioprospecting medicines or poisons remains of pivotal importance. Indian Ayurvedic and traditional Chinese systems are living ‘great traditions’. Ayurvedic knowledge and experiential database can provide new functional leads to reduce time, money and toxicity - the three main hurdles in the drug development. We begin the search based on Ayurvedic medicine research, clinical experiences, observations or available data on actual use in patients as a starting point. We use principles of systems biology where holistic yet rational analysis is done to address multiple therapeutic requirements. Since safety of the materials is already established from traditional use track record, we undertake pharmaceutical development, safety validation and pharmacodynamic studies in parallel to controlled clinical studies. Thus, drug discovery based on Ayurveda follows a ‘Reverse Pharmacology’ path from Clinics to Laboratories. Herein we describe such approaches with selected examples based on previous studies.

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Keywords: Ayurveda; Reverse pharmacology; adaptogens; adjuvants; chemoprotection; drug discovery

Document Type: Research Article

Publication date: December 1, 2008

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  • The journal aims to provide updates to researchers about new bioactive compounds with proven activities in various biological screenings and pharmacological models. The journal will contain information about the structures, biological activities and sources of chemical entities discovered or designed by researchers and published in leading journals. The aim is to provide a valuable information source of bioactive compounds synthesized or isolated, which can be used for further development of pharmaceuticals by industry and academia.

    The journal should prove to be essential reading for pharmacologists, pharmaceutical chemists and medicinal chemists who wish to be kept informed and up-to-date with the latest and most important developments about new bioactive compounds of natural or synthetic origin, including recent patents.
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