Izuforant

Izuforant (JW1601) (Compound 24) is an orally active histamine H4 receptor (H4R) antagonist with an IC50 of 36 nM against human H4R. Izuforant also shows binding affinity of human serotonin 3 receptor (h5-HT3R) with an IC50 of 9.1 μM. Izuforant exhibits strong anti-pruritic and anti-inflammatory efficacies[1][2].

Signaling Pathways >> Immunology/Inflammation >> Histamine Receptor

Research Areas >> Inflammation/Immunology

Signaling Pathways >> GPCR/G Protein >> Histamine Receptor

Human H4 Receptor:36 nM (IC50)

h5-HT3R:9.1 μM (IC50)

Izuforant (JW1601) (Compound 24) shows metabolic stability with CLh,int values of 3.05 and 1.33 mL/min/mg in mouse and human, respectively[1].

Izuforant (JW1601) (50 mg/kg; p.o.; once) decreases histamine-and substance P-induced itching in mice[1]. Izuforant (100 mg/kg; p.o.; twice a day for 3 weeks) inhibits oxazolone-induced atopic dermatitis in mice[1]. Animal Model: Female, ICR mice (8 weeks old)[1] Dosage: 50 mg/kg Administration: Oral administration, once Result: Decreased histamine-and substance P-induced itching. Animal Model: Female, Balb/c mice (6 weeks old, 20±3 g)[1] Dosage: 100 mg/kg Administration: Oral administration, twice a day for 3 weeks Result: Inhibited oxazolone-induced atopic dermatitis (51.2% inhibition). Animal Model: ICR mouse (20~30 g) and SD rat (200~300 g)[1] Dosage: 50 mg/kg for mice and 10 mg/kg for rats Administration: Oral administration (Pharmacokinetic Analysis) Result: Pharmacokinetics parameter of Izuforant (Compound 24)[1] Compound Mouse Rat t1/2 (h) Cmax (μg/mL) AUCinf (μg•hr/mL) t1/2 (h) Cmax (μg/mL) AUCinf (μg•hr/mL) Izuforant 0.96 18.87 32.17 1.30 2.42 4.51

[1]. Pil Su Ho, et al. Novel heterocyclic derivatives and their uses. WO2013048214A2.

[2]. Jin M, et al. From Bench to Clinic: the Potential of Therapeutic Targeting of the IL-22 Signaling Pathway in Atopic Dermatitis. Immune Netw. 2018 Dec 19;18(6):e42.