Rathnam Chaguturu

Center for Advanced Drug research, SRI International, Harrisonburg, Virginia 22802, USA

Abstract:

Decoding of the human genome has not lived up to the hype in providing new drug targets. The promise of pharmacogenomics in paving the path for better, safer drugs has not yet been delivered. Pharmaceutical R&D spending is escalating, but without an avalanche of new drugs in the horizon. Pharmaceutical industry is looking backwards to the golden age of phenotypic-based drug discovery and drug repurposing to ease the drug discovery bottleneck. To uncork the bottleneck, pharmaceutical industry has embraced ‘a problem shared is a problem solved’ paradigm to engage in ‘open source’ drug discovery through a systems biology approach. Industry-style probe discovery has now gained unparalleled momentum in academia with the availability of vendor-supplied chemical libraries and ready access to institutional HTS laboratories. With increased emphasis on high throughput screening and combinatorial chemistry, and the clarity that target-based research provides with regards to the site of action as well as intellectual property, there has been a de-emphasis on natural-product based drug discovery programs over the last 20 years. The wealth of chemical diversity that has evolved with biological diversity is underrepresented in the commercial chemical library offerings, but needs to be harnessed in earnest to ease the current drug discovery bottleneck.It is not coincidental, however, to recognize the fact that there has been a sharp decline in the number of NCEs entering the drug development pipeline over the last 10 to 15 years, with an all-time low of 19 NCEs in 2007, while the major pharmaceutical companies gradually deemphasized their natural-products based lead optimization programs. Many barriers exist for the discovery and development of drugs from natural resources, including bureaucratic and legislative hurdles to access biodiversity, little investment on R&D and innovation by the local governments, and the lack of highly trained scientists-especially in HTS technologies, preclinical and clinical studies.  The biodiversity of tropical and subtropical regions of our planet is an untapped reservoir for searching useful compounds for the benefit of mankind.The talk elucidates the changing landscape in drug discovery as ever more promising, and perhaps the colloquial ‘herding the cats’ may be not that impossible.