Off-target

Off-target refers to the unintended interaction of a therapeutic agent—such as a small molecule drug, monoclonal antibody, or gene-editing tool—with biological molecules other than its primary intended target [14, 15]. In pharmacology, off-target binding occurs when a drug molecule interacts with proteins, receptors, or enzymes that share structural or chemical similarities with the intended target, often leading to adverse drug reactions (ADRs) or unexpected side effects [4, 7, 15]. For example, a drug designed for a specific G protein-coupled receptor (GPCR) might also bind to other GPCR subtypes, causing unintended physiological responses [4]. In the context of gene editing (e.g., CRISPR-Cas9), off-target effects involve the modification of genomic sequences that are homologous to the intended target site, which can result in genotoxicity, chromosomal translocations, or oncogenic transformations [1, 3, 6]. Identifying and minimizing off-target interactions is a critical component of drug safety assessment, lead optimization, and regulatory approval in the pharmaceutical industry [10, 20, 26].

Other names

Off-target effectOff-target bindingNon-specific bindingSecondary pharmacologyUnintended target interaction

Not applicable