ABSTRACT
The modern pharmaceutical industry (Pharma) was built on a foundation of natural products derived from terrestrial actinomycetes isolated from soil. Pharma can trace its major growth phase to the 1950s and 1960s when the “golden age of antibiotics” came to fruition. The prots from marketing these “wonder drugs” propelled the growth and prosperity of Pharma for decades. The lessons learned in antibiotic discovery were translated into the various other therapeutic areas, where numerous unmet medical needs presented great opportunities for drug discovery. The majority of the alternate therapies required much simpler chemistry, and synthetic medicinal chemistry grew into the drug discovery engine that dominates the industry today. In general, Pharma moved away from natural products as a drug discovery platform to structural design and analogue synthesis (me too) as an effective means for generating new commercial products. This transition was essentially complete when the tools of molecular biology that enabled the facile production of single biochemical targets (enzymes, receptors, etc.) were paired with extensive synthetic chemical libraries generated by combinatorial chemistry. Thus began the era of programmed drug discovery that starts with “hits” generated via high-throughput screening (HTS) against single biochemical
CONTENTS
18.1 Historical Perspective ........................................................................................................... 531 18.2 NCDDG and ICBG Programs .............................................................................................. 533 18.3 Changing Landscape of Drug Discovery: Moving Targets .................................................. 534 18.4 Marine Microbial Revolution ............................................................................................... 535 18.5 Genetic Engineering and Genomics ..................................................................................... 536 18.6 Outlook ................................................................................................................................. 537 References ...................................................................................................................................... 538
targets, followed by chemical engineering of potent and selective leads that would be optimized and developed as clinical candidates.
