Poster: Comparing DEL and HTS: Case studies with two unique success stories

Abstract

DNA-encod­ed library (DEL) selec­tions and high-through­put screens (HTS) offer dif­fer­ent means to iden­ti­fy new mol­e­cules for drug dis­cov­ery, each hav­ing their own advan­tages and lim­i­ta­tions. Both meth­ods have been used in count­less suc­cess­ful cam­paigns and often either approach could be a viable way to pur­sue hit iden­ti­fi­ca­tion depend­ing on the project and if the assay and/​or tar­get pos­es any method spe­cif­ic chal­lenges. Some of these chal­lenges can be antic­i­pat­ed, such as DNA bind­ing pro­teins caus­ing non-lig­and depen­dent enrich­ment in DEL selec­tions or pan-assay inter­fer­ence com­pounds in HTS. How­ev­er, oth­er prob­lems are more dif­fi­cult to pre­dict and are only iden­ti­fied ret­ro­spec­tive­ly. We have encoun­tered projects where either the DEL cam­paign or the HTS cam­paign was suc­cess­ful, but the oth­er was not. These out­comes high­light the fact that DEL and HTS have their own unique chal­lenges. As a result, the best approach to ensure a suc­cess­ful hit iden­ti­fi­ca­tion pro­gram is to eval­u­ate con­cur­rent DEL and HTS cam­paigns. To bet­ter under­stand unfore­seen chal­lenges in DEL and HTS, here we dis­cuss two case stud­ies: one where DEL was suc­cess­ful and HTS was not, and anoth­er where HTS was suc­cess­ful and DEL was not.