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, ternary complex of ligand-receptor-transducer) Allosteric ligand a ligand that binds distinct, non-overlapping receptor site(s) relative to the endogenous (natural) ligand Allosteric modulation the ability of an allosteric ligand to augment or inhibit the signaling of another ligand when co-occupying the receptor Antagonist a ligand that binds the receptor and prevent conformational shifts, thereby preventing receptor signaling from going above or below basal levels Biased signaling or functional selectivity signal transduction through only a subset of a receptor’s possible intracellular signaling pathways Constitutive activity receptor-mediated signaling that occurs independent of ligand binding (basal activity) Cryogenic electron microscopy (cryo-EM) an experimental technique using electron microcopy to determine the three-dimensional molecular structure of proteins stabilized in cryogenically frozen grids ECL2 Cap a portion of ECL2 that sits over top the ligand binding pocket in the transducer-coupled conformational state G protein-coupled receptor kinase (GRK) a family of kinases that phosphorylate the C-terminal tail of GPCRs to increase βarr recruitment and binding to the receptor G protein-coupled receptor (GPCR) a large family of integral membrane proteins that control myriad physiological processes and are the most common pharmaceutical drug target Growth hormone secretagogue a stimulus that increased growth hormone secretion Heterodimer a physical interaction between two different proteins Homodimer a physical interaction between two identical proteins Insulinostatic a stimulus that inhibits insulin secretion Insulinotropic a stimulus that increases insulin secretion Inverse Agonist a ligand that stabilizes an inactive conformation and elicits signal transduction below basal levels Ligand bias the process whereby a ligand stabilizes a receptor conformation that disproportionally affects (activates or inhibits) signaling through only a subset of all possible signal transduction pathways Negative energy balance when energy expenditure exceeds energy intake ( e.g

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The dose escalation design tested different starting doses (2 mg vs 4 mg) to evaluate tolerability