Whole cells

The term "Whole cells" refers to the use of intact, living cellular systems as the focus of pharmacological evaluation, typically within phenotypic drug discovery frameworks [1, 2]. Unlike target-based approaches that focus on a specific isolated protein or enzyme, whole-cell assays measure the complex biological response of an organism to a compound in a physiologically relevant environment [3, 4]. This designation is commonly used in biological databases to categorize drugs and screens where the specific molecular mechanism of action is either unknown or involves the orchestration of multiple pathways [11, 13]. While whole-cell screening is highly effective for discovering compounds that are cell-permeable and biologically active, it is not a discrete molecular target but rather a system-level model [5]. Consequently, it is often viewed as a non-specific or "incorrect" target entry in molecular drug databases because it lacks the specificity required for precision pharmacology [11, 13]. The use of whole cells as a primary focus has historically led to the discovery of major therapies, including various antibiotics and immunosuppressants, by focusing on global outcomes such as growth inhibition or apoptosis [1, 5]. However, this approach presents significant challenges in determining exact structure-activity relationships and assessing potential off-target safety risks during development [4, 5].

Other names

Intact cellsCell-based assay targetPhenotypic targetLiving cellsCell culture

Drugs categorized under this target typically act via phenotypic modulation, where the specific molecular targets are often unknown or involve multiple pathways that collectively produce a therapeutic effect like cell death or growth arrest [1, 3, 13].