Various off-target proteins

Various off-target proteins is a collective term used in pharmacology to describe biological entities that interact with a drug molecule other than its intended primary therapeutic target (Bowes et al., 2012). These unintended interactions often arise due to structural similarities between the primary target and other proteins, or high systemic concentrations of the drug that lead to non-specific binding (Lounkine et al., 2012). Common examples of off-targets include the hERG (KCNH2) potassium channel, which is associated with cardiotoxicity, and various Cytochrome P450 enzymes involved in drug metabolism (Sanguinetti & Tristani-Firouzi, 2006). While off-target binding is a major cause of adverse drug reactions and clinical trial failures, it can also provide opportunities for drug repurposing if the secondary interaction yields a beneficial therapeutic effect (Pushpakom et al., 2019). Consequently, safety pharmacology profiling against a panel of antitargets is a standard requirement in modern drug development to mitigate risks of toxicity (Whitebread et al., 2005).

Other names

Off-targetsAntitargetsNon-specific targetsSecondary targetsPromiscuous targets

Unintended binding or modulation of proteins outside the primary therapeutic pathway, often due to structural similarities or high drug concentrations (Bowes et al., 2012).