Izuforant (JW1601) (Compound 24) exhibits potent anti-inflammatory and anti-pruritic activities, with a binding affinity for human serotonin 3 receptor (h5-HT3R) and an IC50 value of 9.1 μM. It is also an orally active antagonist of histamine H4 receptor (H4R), showing an IC50 value of 36 nM against human H4R [1] [2].

5-HT3 receptor:9.1 μM, H4 receptor (human):36 nM

Izuforant (JW1601) (Compound 24) exhibits metabolic stability, with clearance rates (CL h,int) of 3.05 mL/min/mg in mice and 1.33 mL/min/mg in humans, indicating efficient metabolism across these species [1].

Izuforant (JW1601) administered orally at a dosage of 50 mg/kg once, effectively mitigates histamine-and substance P-induced itching in mice, while a higher dose of 100 mg/kg given twice daily for three weeks successfully attenuates oxazolone-induced atopic dermatitis in mice, demonstrating a 51.2% inhibition rate. This is observed in studies involving female ICR and Balb/c mice specifically aged 8 weeks and 6 weeks respectively, weighing 20±3 g. Additionally, pharmacokinetic analysis in both ICR mice and SD rats, with doses respective to their species (50 mg/kg for mice, 10 mg/kg for rats), reveals the compound's absorption and elimination profiles, marked by its half-life, maximum concentration (Cmax), and area under the curve (AUCinf), thus indicating the compound's effective duration and exposure in the body.