911417-87-3

KD 025 is an inhibitor of Rho-associated kinase 2 (ROCK2; IC₅₀ = 0.105 μM). It is selective for ROCK2 over ROCK1 (IC₅₀ = 24 μM). KD 025 (10 μM) decreases the expression of connective tissue growth factor (CTGF) and induces remodeling of the actin cytoskeleton in isolated human ileal fibrotic smooth muscle cells. It inhibits heat-killed C. albicans- or S. epidermidis-induced production of IL-17 in isolated human peripheral blood mononuclear cells (PBMCs) when used at concentrations ranging from 1.25 to 10 μM. KD 025 (100 and 200 mg/kg) reduces infarct volume in a mouse model of cerebral ischemia induced by transient middle cerebral artery occlusion (MCAO). It decreases disease severity in a mouse model of sclerodermatous chronic graft versus host disease (GVHD) when administered at a dose of 150 mg/kg. Formulations containing KD 025 have been used in the treatment of chronic GVHD.

KD 025 is an inhibitor of Rho-associated protein kinase II (ROCK-II), a serine/threonine kinase that regulates the formation of actin stress fibers and focal adhesions, smooth muscle contraction, and gene expression (1, 2). KD025 has been shown to reduce infarct volume after transient middle cerebral artery occlusion (2).

Rezurock

Class: serine-threonine kinase; Treatment: chronic GVHD; Other name: SLx-2119, KD025; Oral bioavailability = 64%; Elimination half-life = 19 h; Protein binding = 99.9%

Primary target: ROCK2

Boerma et al. (2008) Comparative gene expression profiling in three primary human cell lines after treatment with a novel inhibitor of Rho kinase or atorvastatin; Blood Coagul. Fibrinolysis.?19 709 Zanin-Zhorov et al. (2014) Selective oral ROCK2 inhibitor down-regulates IL-21 and IL-17 secretion in human T cells via STAT3-dependent mechanism; Natl. Acad. Sci. USA?111 16814 Flynn et al. (2016) Targeted Rho-associated kinase 2 inhibition suppresses murine and human chronic GVHD through a Stat3-dependent mechanism; 127 2144 Jagasia et al. (2021) ROCK2 Inhibition with Belumosudil (KD025) for the Treatment of Chronic Graft-Versus-Host Disease; Clin. Invest.?39 1888 Diep et al. (2018) Anti-adipogenic effects of KD025 (SLx-2119), a ROCK2-specific inhibitor, in 3T3-L1 cells; Rep.?8 2477 Diep et al. (2019) KD025 (SLx-2119) suppresses adipogenesis at intermediate stage in human adipose-derived stem cells; Adipocyte?9 114 Wei et al. (2020) ROCK2 inhibition enhances the thermogenic program in white and brown fat tissue in mice; FASEB J.?34 474 Tran and Chun (2021) ROCK2-Specific Inhibitor KD025 Suppresses Adipocyte Differentiation by Inhibiting Casein Kinase 2; Molecules?26 4747