INCB38579 is an orally active, highly brain penetrable, and selective histamine H4 receptor (HH4R) antagonist (hH4R IC50=4.8 nM, mH4R IC50=42 nM, rH4R IC50=32 nM). INCB38579 shows anti-inflammatory pain and anti-pruritic activities[1].
INCB38579 (0.1 nM-10 μM; 1.5 h) inhibits histamine binding to the recombinant human and rodent histamine H4 receptors[1].
INCB38579 (0.1 nM-10 μM; 20 min) blocks histamine-induced migration of dendritic cells differentiated from human monocytes and mouse bone marrow cells[1].
NCB38579 (0-30 nM; 1.5 h) inhibits histamine-induced cell shape change and migration of purified human eosinophils dose-dependently[1].
Cell Viability Assay[1]
| Cell Line: | HEK293 cells |
| Concentration: | 0.1 nM-10 μM |
| Incubation Time: | 1.5 hours |
| Result: | Showed the IC50 values of 4.8, 42 and 21 nM for the human, mouse and rat histamine H4 receptors, respectively. |
Cell Viability Assay[1]
| Cell Line: | Human monocytes, mouse bone marrow cells, and human eosinophils |
| Concentration: | 0.1 nM-10 μM |
| Incubation Time: | 20 min |
| Result: | Showed IC50s of 13.2 and 77 nM for human monocytes and mouse bone marrow cells，respectively. Showed IC50 values of approximately 20-30 nM for purified human eosinophils. |
Cell Viability Assay[1]
| Cell Line: | HEK293 cells |
| Concentration: | 0-30 nM |
| Incubation Time: | 1.5 hours |
| Result: | Showed the IC50 values of 4.8, 42 and 21 nM for the human, mouse and rat histamine H4 receptors, respectively. |
INCB38579 (oral gavage; 100 mg/kg; once) inhibits histamine-mediated pruritus in mice[1].
INCB38579 (oral gavage; 100 mg/kg; once) shows antinociceptive functions in this acute model of inflammatory pain[1].
INCB38579 (oral gavage; 3, 10, 30, and 100 mg/kg; once) inhibits formalin-induced pain in rats and mice[1].
| Animal Model: | Female CD-1 mice histamine-induced pruritus[1] |
| 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[1] |
| 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[1] |
| 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. |