The approaches and concepts that encompass combinatorial chemistry represent a paradigm shift in drug discovery and basic research.  Viewed initially as a curiosity by the pharmaceutical industry, combinatorial chemistry approaches are now recognized as essential drug discovery tools that decrease the time taken for discovery and increase the throughput of chemical screening by as much as 1000-fold.  Although the use of mixture-based synthetic combinatorial libraries was one of the first approaches presented, its inherent strengths are only recently being recognized.  Numerous mixture-based libraries of peptides, peptidomimetics and heterocycles have been synthesized and deconvoluted using the positional scanning approach.  Mixture-based library approaches for discovery using both in vitro and direct in vivo testing for drug discovery and development of high value therapeutic hits will be discussed. 

Houghten, R.A.; Pinilla, C.; Appel, J.R.; Blondelle, S.E.; Dooley, C.T.; Eichler, J.; Nefzi, A.; Ostresh, J.M. J. Med. Chem. 1999, 42, 3743; Nefzi, A.; Ostresh, J.O. and Houghten, R.A. 2004. J. Org. Chem., 69: 3603-3609; Houghten, R.A.Dooley, C.T. and Appel, J.R. 2006. AAPS Journal; 8(2) Article 42(http://www.aapsj.org.