PARP14 inhibitor 1

BALB/c mice with Atopic dermatitis (male, n=6 per group, DNCB-induced atopic dermatitis model)^[1]

30 mg/kg; 90 mg/kg; 270 mg/kg

p.o.; daily; ~14 days

Reduced dermatitis scores in a dose-dependent manner, with the 90 mg/kg group showing greater improvement than a positive control reference group, and the 270 mg/kg group showing efficacy comparable to another positive control reference group.
Mitigated histopathological skin changes (thickened epidermis/dermis, hyperkeratosis, collagen degeneration, vasodilation, inflammatory cell infiltration) in a dose-dependent manner, with the 270 mg/kg group achieving a histological score similar to the Upadacitinib reference group and superior to the RBN-3143 reference group.
Significantly decreased skin protein levels of IL-4, IL-13, and IL-17A, and serum IgE levels in 90 mg/kg and 270 mg/kg groups, with the 270 mg/kg group showing the lowest cytokine levels.
Reduced skin mRNA expression of IL-4, IL-13, and IL-17A in a dose-dependent manner; the 90 mg/kg group showed greater efficacy than the RBN-3143 (HY-150207) group, and the 270 mg/kg group showed efficacy comparable to the Upadacitinib (HY-19569) group.
Most effectively reduced skin mRNA expression of TSLP and GATA3 in the 270 mg/kg group, with weak regulation of IL-33 mRNA levels.
Showed no significant body weight loss during the study.