861998-00-7

Ki: 0.7 nM (ghrelin receptor)
EC50: 0.74 nM (ghrelin receptor)

In the FLIPR assay, Anamorelin (ANAM) shows significant agonist activity on the ghrelin receptor, with EC ₅₀ value of 0.74 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 (K _i ) of 0.70 nM. In the competition assay with radiolabeled ibutamoren ( ³⁵ S-MK-677; another ghrelin receptor agonist) Anamorelin (ANAM) is also found to bind with high affinity to the ghrelin receptor (IC ₅₀ =0.69 nM). In rat pituitary cells incubated with Anamorelin, there is a dose-dependent stimulatory effect on GH release and the potency (EC ₅₀ ) 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 (NK ₂ ) site (IC ₅₀ =0.021 μM); however, a subsequent NK ₂ functional assay demonstrates no functional activity.

In rats, Anamorelin (ANAM) 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 (P<0.05) 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 AUC _0-6h in rats.