ROCK

ROCK2-IN-14 is an orally bioavailable and selective ROCK2 inhibitor with an IC₅₀ of 4.8 nM, and it is 212 times more selective for ROCK2 over ROCK1 (IC₅₀=1.01 μM). By inhibiting the ROCK2/S100A9 signaling pathway, ROCK2-IN-14 reduces S100A9 expression, inhibits NM2 phosphorylation, and corrects cytoskeletal abnormalities. Consequently, it lowers levels of inflammatory cytokines, alleviates skin inflammation, and exhibits anti-inflammatory effects. In atopic dermatitis (AD) mouse models, ROCK2-IN-14 significantly reduces ear thickening and decreases IgE, TNF-α, IL-6, and TSLP levels. The compound demonstrates good safety, with a maximum tolerable oral dose exceeding 500 mg/kg, making it a potential candidate for atopic dermatitis research.

Rhodblock 1a is an inhibitor of the Rho kinase signaling pathway, which disrupts the localization and function of proteins within the Rho pathway. This interference hinders the proper formation of the cleavage furrow during cell division, leading to some cells either failing to form the cleavage furrow or forming a ruptured furrow, resulting in binucleated cells. Rhodblock 1a can be utilized for investigating cell division mechanisms and holds potential for research into cardiovascular diseases and cancer.

ROCK-IN-11 (example 94) is an effective inhibitor of ROCK1 and ROCK2, with an IC₅₀ of ≤ 5 μM, and plays a significant role in cancer research.

NRL-1049 dihydrochloride (BA-1049) is an orally active and selective inhibitor of Rho-associated protein kinase 2 (ROCK2) with an IC₅₀ value of 0.59 μM. It demonstrates a 44-fold selectivity for ROCK2 over ROCK1, which has an IC₅₀ value of 26 μM. NRL-1049 dihydrochloride can protect the blood-brain barrier following acute injury.

ROCK2-IN-12 (Compound A25) is a selective inhibitor of ROCK2, exhibiting an IC₅₀ of 7.0 nM for ROCK2, demonstrating greater efficacy compared to ROCK1 inhibition. It exerts potent anti-fibrotic effects via the TGF-β/Smad and ROCK2/STAT3 signaling pathways. In a Bleomycin-induced mouse pulmonary fibrosis (PF) model, ROCK2-IN-12 significantly reduces collagen deposition and reverses fibrosis progression. This compound is applicable in research on pulmonary diseases such as lung fibrosis.

Zelasudil (RXC007) is a Rho-related (ROCK) kinase inhibitor for the study of idiopathic pulmonary fibrosis and inflammation.