Home Cell Cycle ROCK inhibitor Belumosudil (KD025) For research use only.

Belumosudil (KD025)

Synonyms: SLx-2119

Belumosudil (KD025, SLx-2119) is an orally available, and selective ROCK2 inhibitor with IC50 and Ki of 60 nM and 41 nM, respectively. Phase 2.

Belumosudil (KD025) Chemical Structure

Belumosudil (KD025) Chemical Structure

CAS No. 911417-87-3

Purity & Quality Control

Belumosudil (KD025) Related Products

Signaling Pathway

ROCK Signaling Pathways

ROCK Signaling Pathway

Biological Activity

Description Belumosudil (KD025, SLx-2119) is an orally available, and selective ROCK2 inhibitor with IC50 and Ki of 60 nM and 41 nM, respectively. Phase 2.
Targets
ROCK2 [1]
(Cell-free assay)		 ROCK2 [1]
(Cell-free assay)
41 nM(Ki) 60 nM
In vitro
In vitro

KD025 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. [2]

KD025 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. [3]
Kinase Assay Recombinant ROCK1 and ROCK2 assays
Compound dilutions and reactions are performed in 96-well polystyrene low-binding plates. Filtration is done in 96-well filter plates containing hydrophilic phospho-cellulose cation exchanger membranes. Enzymatic activity of the recombinant ROCK1 and ROCK2 is measured radiometrically in 50 μL of reaction mixture containing assay buffer (50 mmol/L Tris, pH 7.5, 0.1 mmol/L ethyleneglycoltetraacetic acid, 10 mmol/L magnesium acetate and 1 mmol/L dithiothreitol).. The reaction is incubated for 45 min at room temperature and stopped with 25 μL of 3% phosphoric acid. Phosphorylated long S6 peptide is separated from unreacted [[gamma]-33P]ATP by filtration of the quenched reaction contents through a P30 phosphocellulose filter plate. Each filter is washed three times with 75 μL of 75 mmol/L phosphoric acid and one time with 30 μL of 100% methanol. Filter plates are allowed to dry and 30 μL of OptiPhase ‘SuperMix’ scintillation fluid is added to each well. 33Phosphorous is quantified in an I450 MicroBeta scintillation counter and corrected by subtracting the radioactivity associated with the background samples. Data are analyzed and expressed as percent inhibition using the formula ((U − B)/(C − B)) × 100 where U is the unknown value, B is the average of staurosporine background wells, and C is the average of control wells. Curve fitting is performed by GraphPad Prism software using sigmoidal dose-response (variable slope) equation type analysis to generate IC50 values. Ki values are calculated from an equation of Ki = IC50/(1 + [S]/Km)), where [S] and Km are the concentration of ATP and the Km value of ATP, respectively.
Cell Research Cell lines A7r5 cells
Concentrations 10 µM
Incubation Time 2 h
Method

Cells were treated with KD025 for 2 hours.
Experimental Result Images Methods Biomarkers Images PMID
Western blot pSTAT3 / Bcl6 / pSTAT5 / Blimp1 27436361
ELISA IL-21 / IL-17 / IFN-γ 25385601
In Vivo
In vivo

In mice, KD025 (200 mg/kg, p.o.) inhibits ROCK activity in brain and heart, as measured by the degree of MYPT1 phosphorylation. KD025 (200 mg/kg, p.o.) significantly reduces the area of perfusion defect, and reduces tissue loss in the ipsilateral hemisphere. [1]

In a collagen-induced arthritis (CIA) mouse model, KD025 (200 mg/kg, i.p.) downregulates the progression of collagen-induced arthritis via targeting of the Th17-mediated pathway. [2]

KD025 ()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. [3]
Animal Research Animal Models Young adult, aged, or type 2 diabetic mice
Dosages 300 mg/kg
Administration p.o.
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT03919799 Terminated
System; Sclerosis|Diffuse Cutaneous Systemic Sclerosis
Kadmon a Sanofi Company|Sanofi
 June 26 2019 Phase 2
NCT02841995 Completed
Graft vs Host Disease
Kadmon a Sanofi Company|Sanofi
 September 15 2016 Phase 2
NCT02557139 Completed
Bioavailability
Kadmon Corporation LLC|Quotient Clinical
 September 2015 Phase 1
NCT02317627 Completed
Psoriasis Vulgaris
Kadmon Corporation LLC
 December 2014 Phase 2

Chemical Information & Solubility

Molecular Weight 452.51 Formula

C26H24N6O2
CAS No. 911417-87-3 SDF Download Belumosudil (KD025) SDF
Smiles CC(C)NC(=O)COC1=CC=CC(=C1)C2=NC3=CC=CC=C3C(=N2)NC4=CC5=C(C=C4)NN=C5
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 90 mg/mL ( (198.89 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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