Drug Designing: Open Access
Open Access

Drug discovery efforts mirror the proverbial hyper cycle: What’s next?

International Conference and Expo on Drug Discovery & Designing

August 11-13, 2015 Frankfurt, Germany

Rathnam Chaguturu

Posters-Accepted Abstracts: Drug Des

Abstract :

The process of drug discovery has benefited in the past decade by the advent and rise of high-throughput screening (HTS), an early
and vital step of screening small molecule libraries primarily through biochemical and cell-based assays. While the discovery of
new therapeutic drug targets in the post-human-genome-sequencing era is at an all time high, the introduction of new molecular
entities against therapeutic targets is at an all-time low. HTS gained popularity and prominence as a means to that end. Central
to every HTS endeavor is the compound collection. 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. These library
collections are designed and selected for drug-like properties and structural diversity, which is critical to identifying unique hits to
screening targets. Millions of compounds are now commercially available. Both academia and Pharma are engaged in screening large
compound libraries, corporate databases, virtual compound collections and suppliers’ databases for lead drug candidates. Although
the 11 million-plus compounds that comprise the vendor-supplied chemical libraries are designed with a biogenic bias, almost
eighty percent of the core ring scaffolds present among the natural products are surprisingly absent in the commercially available
molecules, and by extension, the screening libraries. While statistically defined chemical space is similar for natural products and
marketed drugs, the combinatorially-derived chemical libraries do not share similar space. Compared to the natural products, the
combinatorially-derived chemical libraries are almost devoid of chiral centers, low on oxygen atoms and rich in nitrogen-the key
features that dictate target selectivity, specificity, and in-vivo metabolism. The wealth of chemical diversity that has evolved with
biological diversity is under represented in the commercial chemical library offerings, but needs to be harnessed in earnest to ease
the current drug discovery bottleneck. Since the chemical diversity of these libraries is not always relevant to biological function, an
earnest plea is being made to the chemical library vendors to advance the chemical methodology and library development technology
platform to increase the natural product-like attributes to play their part in improving the success of our lead finding efforts.