Physical Sciences and Mathematics Commons^™

Direct Phenotypic Screening In Mice: Identification Of Individual, Novel Antinociceptive Compounds From A Library Of 734 821 Pyrrolidine Bis-Piperazines, Richard A. Houghten, Michelle L. Ganno, Jay P. Mclaughlin, Colette T. Dooley, Shainnel O. Eans Torrey Pines Institute For Molecular Studies, Radleigh Santos, Travis Lavoi, Adel Nefzi, Greg Welmaker, Marc A. Giulianotti, Lawrence Toll

Mathematics Faculty Articles

The hypothesis in the current study is that the simultaneous direct in vivo testing of thousands to millions of systematically arranged mixture-based libraries will facilitate the identification of enhanced individual compounds. Individual compounds identified from such libraries may have increased specificity and decreased side effects early in the discovery phase. Testing began by screening ten diverse scaffolds as single mixtures (ranging from 17 340 to 4 879 681 compounds) for analgesia directly in the mouse tail withdrawal model. The “all X” mixture representing the library TPI-1954 was found to produce significant antinociception and lacked respiratory depression and hyperlocomotor effects using …