tcsc6387 Rolapitant

Rolapitant (SCH619734) is a potent, selective and orally active neurokinin NK1 receptor antagonist with a K_i of 0.66 nM.

IC50 & Target: Ki: 0.66 nM (neurokinin)^[1]

In Vitro: Rolapitant has a high affinity for the human NK1 receptor with a K_i of 0.66 nM and high selectivity over the human NK2 and NK3 subtypes of more than 1000-fold, as well as preferential affinity for human, guinea pig, gerbil and monkey NK1 receptors over rat, mouse and rabbit^[1].

In Vivo: Rolapitant reverses NK1 agonist-induced foot tapping in gerbils following both intravenous and oral administration up to 24 hours at a minimal effective dose (MED) of 0.1 mg/kg. Rolapitant is active at 0.1 and 1 mg/kg in both acute and delayed emesis models in ferrets, respectively, consistent with clinical data for other NK1 antagonists. Clinical efficacy of anti-emetics is highly correlated with efficacy in the ferret emesis model, suggesting rolapitant is a viable clinical candidate for this indication^[1].