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, oral administration of Anamorelin at doses of 3, 10, or 30 mg/kg once daily significantly enhanced food intake and body weight from Day 2 to Day 7 of treatment, compared to the vehicle control. The observed increases in food consumption and weight gain were dose-dependent and statistically significant across all dosage levels when compared to the control group. Additionally, a single oral dose of Anamorelin at 3, 10, or 30 mg/kg resulted in a dose-dependent elevation in plasma GH levels and GH AUC0-6h.