Belumosudil

SKU: orb1300393

Description

Belumosudil (Rezurock) is a selective, orally bioavailable ROCK2 inhibitor with an IC50 of 60 nM. It is a research tool for studying Rho-kinase signaling in fibrotic diseases, with applications in both in vitro biochemical assays and in vivo models of chronic graft-versus-host disease.

Research Area

Cardiovascular Research, Immunology & Inflammation

Key Properties

• CAS Number: 911417-87-3
• MW: 452.5
• Purity: >98%
• Formula: C₂₆H₂₄N₆O₂
• SMILES: CC(C)NC(=O)COc1cccc(c1)-c1nc(Nc2ccc3[nH]ncc3c2)c2ccccc2n1
• Target: Kinase
• Solubility: Soluble in DMSO (up to 25 mg/ml)

Bioactivity

• Target IC50:
  ROCK2:41 nM(Ki)|ROCK2:60 nM|ROCK1:24 μM
• In Vivo:
  In mice, Belumosudil (200 mg/kg, p.o.) inhibits ROCK activity in brain and heart, as measured by the degree of MYPT1 phosphorylation. Belumosudil (200 mg/kg, p.o.) significantly reduces the area of perfusion defect, and reduces tissue loss in the ipsilateral hemisphere. In a collagen-induced arthritis (CIA) mouse model, Belumosudil (200 mg/kg, i.p.) downregulates the progression of collagen-induced arthritis via targeting of the Th17-mediated pathway. Belumosudil ()150 mg/kg, i.p. or p.o.) effectively ameliorates cGVHD in a full MHC-mismatch model of multi-organ system cGVHD with bronchiolitis obliterans syndrome and a minor MHC-mismatch model of sclerodermatous GVHD.
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• In Vitro:
  Belumosudil down-regulates the IL-17 and IL-21 secretion in human PBMCs, and leads to down-regulation of STAT3 phosphorylation, IRF4, and RORγt expression in CD4+ T cells. Belumosudil inhibits the secretion of IL-21, IL-17, and IFNγ along with decreasing phosphorylated STAT3 and reduced protein expression of IRF4 and BCL6 in human peripheral blood mononuclear cells.
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• Cell Research:
  SLx-2119 is dissolved in DMSO to obtain a stock solution of 20 mM. Western blots are used to determine whether HMVEC, NHDF and PASMC express ROCK1 and ROCK2. The cells are incubated for 24 hours in 3 mL culture media containing SLx-2119. All cells are collected at passage 3 and lysed on ice in 25 mM Tris-HCl pH 7.5, 150 mM NaCl, 0.5% tritonX-100, 10% glycerol, 10 mM NaF and a protease inhibitor cocktail. Protein concentration is determined using a BCA protein assay reagent. Cell lysates (35 μg) are separated on 7.5% or 12.5% SDS-PAGE polyacrylamide gels and transferred to PVDF membrane filters. Membranes are blocked in 5% non-fat milk in TBS containing 0.1% Tween 20. Blots are probed with antibodies to ROCK1, ROCK2 or actin and washed well before incubation with HRP-conjugated secondary antibodies and visualization with an enhanced chemiluminescence (ECL) kit.
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Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

KD025; SLx-2119

Compound Identifiers

PubChem CID

11950170