Belumosudil(KD025,SLx-2119) - 半岛电竞官方网址

Molecular Weight (MW)	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:>30 mg/mL
Water:<1 mg/mL
Ethanol:<1 mg/mL
SMILES	O=C(NC(C)C)COC1=CC=CC(C2=NC(NC3=CC4=C(NN=C4)C=C3)=C5C=CC=CC5=N2)=C1
Synonyms	Belumosudil; KD-025; SLx-2119; KD025; SLx2119; KD 025; SLx 2119; ROCK inhibitor; Chemical Name: 2-[3-[4-(1H-indazol-5-ylamino)-2-quinazolinyl]phenoxy]-N-(1-methylethyl)-acetamide

Molecular Weight (MW)

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:>30 mg/mL

Water:<1 mg/mL

Ethanol:<1 mg/mL

SMILES

O=C(NC(C)C)COC1=CC=CC(C2=NC(NC3=CC4=C(NN=C4)C=C3)=C5C=CC=CC5=N2)=C1

Synonyms

Belumosudil; KD-025; SLx-2119; KD025; SLx2119; KD 025; SLx 2119; ROCK inhibitor;

Chemical Name: 2-[3-[4-(1H-indazol-5-ylamino)-2-quinazolinyl]phenoxy]-N-(1-methylethyl)-acetamide

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.
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.

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.

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.

CAS NO:	911417-87-3
规格:	≥98%

包装	价格(元)
5mg	电议
10mg	电议
25mg	电议
50mg	电议
100mg	电议
250mg	电议
500mg	电议