Introduction: Strong scientific evidence and large experience support the use of β2-agonists for the symptomatic alleviation of COPD. Therefore, there is considerable effort in discovering highly potent and selective β2-agonists. Areas covered: Recent research on novel β2-agonists for the treatment of COPD. A detailed literature search was performed in two major databases (PubMed/MEDLINE and Scopus) up to September 2023.” Expert opinion: Compounds that preferentially activate a Gs- or β-arrestin-mediated signaling pathway via β- adrenoceptors (ARs) are more innovative. Pepducins, which target the intracellular region of β2-AR to modulate receptor signaling output, have the most interesting profile from a pharmacological point of view. They stabilize the conformation of the β2-AR and influence its signaling by interacting with the intracellular receptor-G protein interface. New bifunctional drugs called muscarinic antagonist-β2 agonist (MABA), which have both muscarinic receptor (mAChR) antagonism and β2-agonist activity in the same molecule, are a new opportunity. However, all tested compounds have been shown to act predominantly as mAChR antagonists or β2-agonists. An intriguing idea is to utilize allosteric modulators that bind to β2-ARs at sites different than those bound by orthosteric ligands to augment or reduce the signaling transduced by the orthosteric ligand.
Advances in adrenergic receptors for the treatment of chronic obstructive pulmonary disease: 2023 update / Matera, M. G.; Rinaldi, B.; Calzetta, L.; Rogliani, P.; Cazzola, M.. - In: EXPERT OPINION ON PHARMACOTHERAPY. - ISSN 1465-6566. - 24:18(2023), pp. 2133-2142. [10.1080/14656566.2023.2282673]
Advances in adrenergic receptors for the treatment of chronic obstructive pulmonary disease: 2023 update
Rinaldi B.;Calzetta L.;Rogliani P.;
2023-01-01
Abstract
Introduction: Strong scientific evidence and large experience support the use of β2-agonists for the symptomatic alleviation of COPD. Therefore, there is considerable effort in discovering highly potent and selective β2-agonists. Areas covered: Recent research on novel β2-agonists for the treatment of COPD. A detailed literature search was performed in two major databases (PubMed/MEDLINE and Scopus) up to September 2023.” Expert opinion: Compounds that preferentially activate a Gs- or β-arrestin-mediated signaling pathway via β- adrenoceptors (ARs) are more innovative. Pepducins, which target the intracellular region of β2-AR to modulate receptor signaling output, have the most interesting profile from a pharmacological point of view. They stabilize the conformation of the β2-AR and influence its signaling by interacting with the intracellular receptor-G protein interface. New bifunctional drugs called muscarinic antagonist-β2 agonist (MABA), which have both muscarinic receptor (mAChR) antagonism and β2-agonist activity in the same molecule, are a new opportunity. However, all tested compounds have been shown to act predominantly as mAChR antagonists or β2-agonists. An intriguing idea is to utilize allosteric modulators that bind to β2-ARs at sites different than those bound by orthosteric ligands to augment or reduce the signaling transduced by the orthosteric ligand.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.