Functional selectivity

<p>Functional selectivity (or “agonist trafficking”, “biased agonism”, “biased signaling”, "ligand bias" and “differential engagement”) is the <a href="/facts/Ligand_(biochemistry)/44QLL4eU">ligand</a>-dependent selectivity for certain <a href="/facts/Signal_transduction/1bs0Me6w">signal transduction</a> pathways relative to a reference ligand (often the endogenous hormone or peptide) at the same <a href="/facts/Receptor_(biochemistry)/tjTAC76a">receptor</a>. Functional selectivity can be present when a receptor has several possible signal transduction pathways. To which degree each pathway is activated thus depends on which ligand binds to the receptor. Functional selectivity, or biased signaling, is most extensively characterized at <a href="/facts/G_protein_coupled_receptors/0arUMkQc">G protein coupled receptors</a> (GPCRs). A number of biased agonists, such as those at muscarinic M2 receptors tested as analgesics or antiproliferative drugs, or those at opioid receptors that mediate pain, show potential at various receptor families to increase beneficial properties while reducing side effects. For example, pre-clinical studies with <a href="/facts/G_protein/HKkcfgGP">G protein</a> biased agonists at the <a href="/facts/%CE%9C-opioid_receptor/8a3wdeTc">μ-opioid receptor</a> show equivalent efficacy for treating pain with reduced risk for addictive potential and <a href="/facts/Respiratory_depression/ruqIr4oa">respiratory depression</a>. Studies within the chemokine receptor system also suggest that GPCR biased agonism is physiologically relevant. For example, a beta-arrestin biased agonist of the chemokine receptor <a href="/facts/CXCR3/IWVPywYW">CXCR3</a> induced greater <a href="/facts/Chemotaxis/hYPRdPTk">chemotaxis</a> of T cells relative to a G protein biased agonist.
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Functional selectivity open-in-new

Functional selectivity