1Agonist

1Agonist is a term used in pharmacology to describe a ligand that acts as an agonist at a single receptor subtype with high selectivity. The prefix "1" signals that the compound principally engages one receptor type in a given experimental context, though the term is informal and not a formal pharmacological category. In practice, a 1Agonist would elicit a full or near-full response at its target receptor while showing minimal activity at other receptors, potentially reducing off-target effects.

Mechanistically, 1Agonists bind to the receptor’s orthosteric site or a highly selective allosteric site and stabilize receptor conformations that promote downstream signaling. The signaling pathway activated depends on the receptor family and can involve G protein–coupled pathways, β-arrestin–mediated routes, or other intracellular cascades.

In research and drug discovery, 1Agonists are valued for their potential to clarify receptor-specific physiology and to serve as lead compounds with improved safety profiles. They are identified through screening and structure–activity relationship studies that optimize affinity, efficacy, and selectivity. Challenges include achieving true single-receptor selectivity in vivo, given conserved binding pockets across receptor subtypes and species differences, as well as achieving favorable pharmacokinetic properties.

Limitations: because "1Agonist" is not a formal designation, practice varies, and researchers may instead refer to a selective full agonist or a subtype-selective agonist. See also: agonist, full agonist, partial agonist, selectivity, receptor pharmacology.