Anamorelin Fumarate is a novel ghrelin receptor agonist (EC50: 0.74 nM in the FLIPR assay).

Ghrelin receptor:（EC50）0.74 nM , Ghrelin receptor:（ki）0.7 nM

No significant antagonist activity is observed with Anamorelin at concentrations of up to 1,000 nM. In the binding experiments, Anamorelin binds to the ghrelin receptor with a binding affinity constant (Ki) of 0.70 nM. In the competition assay with radiolabeled ibutamoren (another ghrelin receptor agonist), Anamorelin is also found to bind with high affinity to the ghrelin receptor (IC50: 0.69 nM). In rat pituitary cells incubated with Anamorelin, there is a dose-dependent stimulatory effect on GH release and the potency (EC50) is 1.5 nM. Anamorelin is screened for activity against a set of over 100 receptors, ion channels, transporters, and enzymes. Anamorelin demonstrates binding to the tachykinin neurokinin 2 (NK2) site (IC50: 0.021 μM); however, a subsequent NK2 functional assay demonstrates no functional activity.

In rats, Anamorelin at an oral dose of 3, 10, or 30 mg/kg once daily significantly increases both food intake and body weight from Day 2 to Day 7 of treatment compared with the vehicle control. The cumulative change in food intake and weight gain increases dose-dependently, and these changes are significant at all dose levels compared to the control. Administration of Anamorelin at a single oral dose of 3, 10, or 30 mg/kg induces a dose-dependent increase in plasma GH levels and GH AUC0-6h in rats.