Belumosudil CAS# 911417-87-3 2-[3-[4-[(1H-吲唑-5-基)氨基]喹唑啉-2-基]苯氧基]-N-异丙基乙酰胺

Belumosudil (SLx-2119, KD025) is a selective inhibitor of Rho-associated coiled-coil kinase-2 (ROCK2). In biochemical assays it inhibits ROCK2 with an IC₅₀ of ~60–105 nM and shows >200-fold selectivity over ROCK1 (IC₅₀ ≈3–24 µM). In vitro, belumosudil suppresses inflammatory signaling in human peripheral blood mononuclear cells and CD4⁺ T cells, reducing IL-21 and IL-17 secretion by ~90% and ~60%, respectively, via inhibition of STAT3 phosphorylation and down-regulation of IRF4 and RORγt; it also decreases profibrotic gene expression such as CTGF and TSP-1 in endothelial or smooth-muscle cells. In vivo, belumosudil demonstrates anti-inflammatory and tissue-protective activity in several mouse models: oral doses around 100–300 mg/kg reduce cerebral infarct volume by ~30–40% in transient middle cerebral artery occlusion models, while ~200 mg/kg suppresses disease progression in collagen-induced arthritis and ameliorates chronic graft-versus-host disease by modulating Th17-mediated immune responses