Increasing the odds of hit identification in screening is of significance for drug discovery. The odds for finding a hit are closely related either to the diversity of libraries or to the availability of focused libraries. There are no truly diverse libraries and it is difficult to design focused libraries without sufficient information. Hence it is helpful to consider alternative approaches that can enhance the odds using existing libraries. Multiple members of a protein family have been considered collectively in inhibitor design, on the basis of the correlation between protein families and ligands derived from specific compound classes. Such a correlation has been exploited in various drug discovery studies and a general receptor-homolog-based screening scheme may be devised. The feasibility of such a scheme in enhancing the odds of hit identification is discussed.Singapore-MIT Alliance (SMA)