Biasing the odds: Approaches to capturing, understanding and exploiting functional selectivity in GPCRs

Mu-Opioid receptor biased ligands: A safer and painless discovery of analgesics?

“…As a result, specific pathways are activated with differential efficacies. Such an effect can be induced either by the binding of the ligand to the orthosteric site of the receptor, or by the binding of allosteric modulators that induce biased signaling via the endogenous agonist [27,28]. This is achieved by fine-tuning the conformation of the receptor [27].…”

“…Such an effect can be induced either by the binding of the ligand to the orthosteric site of the receptor, or by the binding of allosteric modulators that induce biased signaling via the endogenous agonist [27,28]. This is achieved by fine-tuning the conformation of the receptor [27]. The key therapeutic feature of biased agonists is their ability to differentiate between specific signaling pathways, aiming to reduce the related adverse effects without compromising therapeutic value (Fig.…”

“…The discovery of molecules with the ability to selectively modulate GPCRs has been described extensively in the literature [27,29–34], supporting and validating the discovery of emerging functionally selective drugs. The increasing number of biased GPCR agonists with potential therapeutic impact is remarkable, as summarized in Table 1.…”