Target agnostic cellular screening in the era of chemically induced proximity

"chemically induced proximity". In many cases, the small molecules enable new protein-protein interactions that do not exist in the native cells, thus creating a "gain-of-function" effect that may not be recapitulated from knock down or knock out methods. In this perspective article, recent findings and their implications for drug discovery are discussed. Additionally, a general framework for target agnostic screening in the context of "chemically induced proximity" is proposed, aiming to maximize the efficiency of hit finding by balancing screening efforts with mechanism-of-action deconvolution, including key factors such as the nature of compounds for screening, assay format, and readout.