Multiple off-target signaling proteins

Multiple off-target signaling proteins is a collective term used in pharmacology to describe a diverse group of proteins that interact with a drug molecule outside of its intended therapeutic target. These interactions typically arise due to structural similarities between the primary target and other proteins, or due to the chemical properties of the drug that allow for non-specific binding across different protein families such as kinases, G protein-coupled receptors (GPCRs), and ion channels (Bowes et al., 2012, Nature Reviews Drug Discovery). While the primary target is intended to mediate the drug's efficacy, interactions with off-target signaling proteins are frequently responsible for unintended biological responses and adverse drug reactions (Lounkine et al., 2012, Nature). In drug development, these off-targets are often referred to as anti-targets when their modulation leads to significant safety concerns, such as the hERG potassium channel's association with cardiac arrhythmias (Whitebread et al., 2005, Drug Discovery Today). The identification and characterization of these proteins are essential components of safety pharmacology and lead optimization to ensure high molecular specificity and a favorable safety profile. Because this term encompasses a wide array of unrelated proteins rather than a single biological entity, it is considered a category of pharmacological concern rather than a specific therapeutic target.

Other names

Off-targetsSecondary targetsAnti-targetsNon-specific targetsCollateral targets

Unintended competitive or non-competitive binding to secondary proteins leading to off-target signaling modulation