INCB38579 (C09-1140-153)

INCB38579 is an orally active, highly brain penetrable, and selective histamine H 4 receptor (HH 4 R) antagonist (hH 4 R IC 50 =4.8 nM, mH 4 R IC 50 =42 nM, rH 4 R IC 50 =32 nM). INCB38579 shows anti-inflammatory pain and anti-pruritic activitiesIn VitroINCB38579 (0.1 nM-10 μM; 1.5 h) inhibits histamine binding to the recombinant human and rodent histamine H 4 receptors. INCB38579 (0.1 nM-10 μM; 20 min) blocks histamine-induced migration of dendritic cells differentiated from human monocytes and mouse bone marrow cells. NCB38579 (0-30 nM; 1.5 h) inhibits histamine-induced cell shape change and migration of purified human eosinophils dose-dependently. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Viability AssayCell Line: HEK293 cells Concentration: 0.1 nM-10 μM Incubation Time: 1.5 hours Result: Showed the IC 50 values of 4.8, 42 and 21 nM for the human, mouse and rat histamine H 4 receptors, respectively. Cell Viability AssayCell Line: Human monocytes, mouse bone marrow cells, and human eosinophils Concentration: 0.1 nM-10 μM Incubation Time: 20 min Result: Showed IC 50 s of 13.2 and 77 nM for human monocytes and mouse bone marrow cells，respectively. Showed IC 50 values of approximately 20-30 nM for purified human eosinophils. Cell Viability AssayCell Line: HEK293 cells Concentration: 0-30 nM Incubation Time: 1.5 hours Result: Showed the IC 50 values of 4.8, 42 and 21 nM for the human, mouse and rat histamine H 4 receptors, respectively.In VivoINCB38579 (oral gavage; 100 mg/kg; once) inhibits histamine-mediated pruritus in mice . INCB38579 (oral gavage; 100 mg/kg; once) shows antinociceptive functions in this acute model of inflammatory pain . INCB38579 (oral gavage; 3, 10, 30, and 100 mg/kg; once) inhibits formalin-induced pain in rats and mice . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Female CD-1 mice histamine-induced pruritus Dosage: 100 mg/kg Administration: Oral gavage; 100 mg/kg; once Result: Reduced the number of scratching bouts significantly (P<0.05). Animal Model: Sprague-Dawley rats injected with carrageenan Dosage: 100 mg/kg Administration: Oral gavage; 100 mg/kg; once Result: Increased the paw withdrawal threshold from a baseline of 61 g to approximately 100 g, achieving approximately 60% in maximal possible effect. Animal Model: Male Sprague–Dawley rats and male ICR mice injected with formalin into the hind paws Dosage: 3, 10, 30, and 100 mg/kg Administration: Oral gavage; 3, 10, 30, and 100 mg/kg; once Result: Showed a significant dose-dependent analgesic effect from 10 to 100 mg/kg in the phase 1 response and 30 to 100 mg/kg in the phase 2 response in the mouse formalin test. Observed a dose-dependent and statistically significant effect in the phase 1 response, ranging from10 to 100 mg/kg, in the rat formalin test.Form:SolidIC50& Target:Human H 4 Receptor 4.8 nM (IC 50 ) Mouse H 4 Receptor 42 nM (IC 50 ) Rat H 4 receptor 21 nM (IC 50 ). Specification: 0.99 Molecular Formula: C25H34N6O Molecular Weight: 434.58