受注:045-509-1970 |
技術サポート:[email protected] 平日9:00〜18:00 1営業日以内にご連絡を差し上げます |
Synonyms | SLx-2119 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
||||
化学式 | C26H24N6O2 |
||||||
分子量 | 452.51 | CAS No. | 911417-87-3 | ||||
Solubility (25°C)* | 体外 | DMSO | 91 mg/mL (201.1 mM) | ||||
Ethanol | 91 mg/mL (201.1 mM) | ||||||
Water | Insoluble | ||||||
体内 (毎回新しく調製した物を用意してください) |
|
||||||
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. |
製品説明 | 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. |
---|---|
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] |
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] |
キナーゼアッセイ | 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). Long S6 peptide (KEAKEKRQEQIAKRRRLSSLRASTSKSGGSQK, 30 μmol/L), ROCK (4 mU per reaction) and ATP (10 μmol/L; 1 μCi [[gamma]-33P]ATP) and test compound are diluted to a final dimethylsulfoxide concentration of 1%. 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. | ||
細胞アッセイ | 細胞株 | A7r5 cells |
濃度 | 10 µM | |
反応時間 | 2 h | |
実験の流れ | Cells were treated with KD025 for 2 hours. |
|
動物実験 | 動物モデル | Young adult, aged, or type 2 diabetic mice |
投薬量 | 300 mg/kg | |
投与方法 | p.o. |
Selectivity matters: selective ROCK2 inhibitor ameliorates established liver fibrosis via targeting inflammation, fibrosis, and metabolism [ Commun Biol, 2023, 10.1038/s42003-023-05552-0] | PubMed: 37980369 |
ROCK1 mechano-signaling dependency of human malignancies driven by TEAD/YAP activation [ Nat Commun, 2022, 13(1):703] | PubMed: 35121738 |
Inhibition of ROCK ameliorates pulmonary fibrosis by suppressing M2 macrophage polarisation through phosphorylation of STAT3 [ Clin Transl Med, 2022, 12(10):e1036] | PubMed: 36178087 |
Phenotypic Screening for Small Molecules that Protect β-Cells from Glucolipotoxicity [ ACS Chem Biol, 2022, 10.1021/acschembio.2c00052] | PubMed: 35439415 |
Pressure and stiffness sensing together regulate vascular smooth muscle cell phenotype switching [ Sci Adv, 2022, 8(15):eabm3471] | PubMed: 35427166 |
The Rho kinase 2 (ROCK2)-specific inhibitor KD025 ameliorates the development of pulmonary arterial hypertension [ Biochem Biophys Res Commun, 2021, 534:795-801] | PubMed: 33160621 |
Selective dysregulation of ROCK2 activity promotes aberrant transcriptional networks in ABC diffuse large B-cell lymphoma [ Sci Rep, 2020, 10(1):13094] | PubMed: 32753663 |
KD025, an anti-adipocyte differentiation drug, enhances the efficacy of conventional chemotherapeutic drugs in ABCG2-overexpressing leukemia cells [ Oncol Lett, 2020, 20(6):309] | PubMed: 33093918 |
Integrated proximal proteomics reveals IRS2 as a determinant of cell survival in ALK-driven neuroblastoma. [ Sci Signal, 2018, 11(557)] | PubMed: 30459283 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。