ROCK2-IN-14 is an orally active, selective ROCK2 inhibitor (IC50=4.8 nM) with 212-fold selectivity over ROCK1 (IC50=1.01 μM). By inhibiting the ROCK2/S100A9 signaling pathway, ROCK2-IN-14 downregulates S100A9 expression, inhibits NM2 phosphorylation and restores cytoskeletal abnormalities. Furthermore, ROCK2-IN-14 reduces inflammatory cytokine levels, alleviates skin inflammation and exerts anti-inflammatory activity. ROCK2-IN-14 also significantly inhibits ear thickening in a mouse model of atopic dermatitis (AD), and decreases the levels of IgE, TNF-α, IL-6 and TSLP. ROCK2-IN-14 has a good safety profile, with a maximum tolerated oral dose exceeding 500 mg/kg. ROCK2-IN-14 can be used for research on atopic dermatitis.
