ABSTRACT
Essentially, no high-throughput formal lead optimization exists in this model but is developed for backup compounds by using biomarkers identified during lead compound failure in vivo. The computational prediction of drug bioavailability has been pioneered by Lipinski's ''Rule of Five,'' which is based on compound molecular size, hydrogen bonding capacity, and lipophilicity. Increasingly sophisticated packages are being developed to analyze compound structure-activity relationships, i.e., ascribing toxicity to certain structures or substructural features. Thus, the use of microarray technology gene expression microarrays to establish gene expression ''fingerprints'' or expression patterns following compound exposure, and thus to develop screening systems for in vitro lead optimization processes, has become attractive to preclinical scientists interested in drug safety. Single nucleotide polymorphisms are single nucleotide differences present throughout the genome, which differ between unrelated individuals. It is clear then that the people are now entering a new era of both lead optimization technology and drug development.
