In the last decade or so, assays in which the drug discovery target is validated in a cellular context have gained enormously in popularity in the biopharm industry, as well as in many academic groups. It is frequently stated that this popularity arises from the fact that target or inhibitor information is obtained in a more physiologically 'relevant' context given that the cellular integrity remains intact. Indeed, numerous technologies have become available, both on the reagent and instrument sides, that greatly facilitate the use, and extend the applications of cell based assays in life science research. Related to this has been the increased adoption of high content screening (as well as high content analysis) methods that clearly attest to the popularity of cell based assays.
However, given that there are now several years of experience in cell based assays in life science research, some questions can legitimately be asked of HCS/HCA techniques in particular, and cell based assays in general. Specifically, how successful have all these cellular approaches been in terms of increasing both the precision of target validation or lead identification and optimization? Does the widespread use of recombinant cells impose inappropriate phenotypic constraints on the pharmacology that is generated in the cellular assay? Would assays of this kind be better undertaken using primary or stem cells?
HCS/HCA techniques also impose restrictions on the type of cell that can be used in the assay, due in part to the analytical difficulties encountered using software algorithms to obtain the data, particularly with cells that are more 'physiological' in nature. One may thus ask the following questions: Although numerous cellular assays are designed for use in a multiplexed format, how many lead identification campaigns are in fact undertaken in such a fashion? Are these assays alternatively finding their niche application in areas of target validation using, for example, RNAi analysis (at one end of the drug discovery spectrum) or in ADME/Tox assays (at the other)?