product name KD025 (SLx-2119)
Description: KD025, also known as KD-025, is a potent, orally available, and selective ROCK2 inhibitor with IC50 and Ki of 60 nM and 41 nM, respectively. In smooth muscle cells isolated from human intestine with radiation-induced fibrosis (RE-SMC), SLx-2119 reduced mRNA level of CTGF. Over-expression of which is associated with fibrotic diseases. While, in SMC isolated from normal human intestine (N-SMC), SLx-2119 didn’t change CTGF mRNA level.
References: Ann Clin Transl Neurol. 2014 Jan 1;1(1):2-14; Proc Natl Acad Sci U S A. 2014 Nov 25;111(47):16814-9.
452.51
Formula
C26H24N6O2
CAS No.
911417-87-3
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 90 mg/mL (198.9 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
other peoduct :
| In Vitro |
In vitro activity: 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. 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. Kinase Assay: Cell-free enzyme assays were performed to determine the selective inhibition of ROCK1 and ROCK2 by SLx-2119. Reactions were performed on non-binding surface microplates. Four mU of human ROCK1 and ROCK2 were used to phosphorylate 30 μM of the synthetic ROCK peptide substrate S6 Long (sequence: KEAKEKRQEQIAKRRRLSSLRASTSKSGGSQK), prepared at American Peptide (Sunnyvale, CA) with the addition of 10 μM ATP, containing 33P-ATP in the presence of 10 mM Mg2+, 50 mM Tris, pH 7.5, 0.1 mM EGTA and 1 mM DTT at room temperature. One unit is the amount of kinase needed to catalyze the transfer of 1 nmol phosphate/min to the peptide. The reactions were allowed to proceed for 45 minutes and then stopped with 3% phosphoric acid to a final concentration of 1%. The reactions were captured on phospho cellulose filtration microplates and washed with 75 mM phosphoric acid and methanol using a vacuum manifold. Phosphorylation was measured on a Perkin-Elmer MicroBeta 1450. Cell Assay: SLx-2119 at 40 μM significantly reduces the mRNA levels of Tsp-1 and CTGF. |
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| 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. 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. 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. |
| Animal model | Type 2 diabetic mice |
| Formulation & Dosage | Dissolved in 0.4% methylcellulose; 300 mg/kg; oral gavage |
| References | Ann Clin Transl Neurol. 2014 Jan 1;1(1):2-14; Proc Natl Acad Sci U S A. 2014 Nov 25;111(47):16814-9. |
