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SLx-2119

现货
Catalog No.
A3825
ROCK2抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 2,000.00
现货
5mg
¥ 1,300.00
现货
10mg
¥ 1,950.00
现货
25mg
¥ 3,950.00
现货

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Background

SLx-2119(KD-025) is a selective inhibitor of ROCK2 with IC50 of 105 nM [1].
Rho-associated protein kinase (ROCK) is a serine-threonine kinase and is involved in regulating cytoskeletal dynamics. It is associated with many intracellular processes, which are relevant to stroke. ROCK2 is the predominant isoform mainly expressed in vasculature and neurons [2].
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 [1].
In focal cerebral ischemia mice, after transient middle cerebral artery occlusion, KD025 reduced infarct volume in a dose-dependant way. And the efficacy maintained for at least 4 weeks. In aged male and female mice, as well as in type 2 diabetes mice, KD025 reduced infarct volume by 34%, 42% and 32% in aged male mice, female mice and diabetic mice respectively compared to vehicle in mice [2].
References:
[1]. Boerma M, Fu Q, Wang J, et al. Comparative gene expression profiling in three primary human cell lines after treatment with a novel inhibitor of Rho kinase or atorvastatin. Blood Coagul Fibrinolysis, 2008, 19(7): 709-718.
[2]. Lee JH, Zheng Y, von Bornstadt D, et al. Selective ROCK2 Inhibition In Focal Cerebral Ischemia. Ann Clin Transl Neurol, 2014, 1(1): 2-14.

文献引用

1. De Silva TM, Modrick ML, et al. "Changes in Cerebral Arteries and Parenchymal Arterioles With Aging: Role of Rho Kinase 2 and Impact of Genetic Background." Hypertension. 2018 Mar 12. pii: HYPERTENSIONAHA.118.10865. PMID:29531174

Chemical Properties

StorageStore at -20°C
M.Wt452.51
Cas No.911417-87-3
FormulaC26H24N6O2
SynonymsSLx 2119;SLx2119;ROCK inhibitor;KD-025
Solubility≥22.65 mg/mL in DMSO, ≥26.4 mg/mL in EtOH with ultrasonic and warming, <2.46 mg/mL in H2O
Chemical Name2-(3-(4-((1H-indazol-5-yl)amino)quinazolin-2-yl)phenoxy)-N-isopropylacetamide
SDFDownload SDF
Canonical SMILESO=C(C([H])([H])OC1=C([H])C([H])=C([H])C(C2=NC3=C([H])C([H])=C([H])C([H])=C3C(N([H])C(C([H])=C4[H])=C([H])C5=C4N([H])N=C5[H])=N2)=C1[H])N([H])C(C([H])([H])[H])([H])C([H])([H])[H]
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

激酶实验 [1]:

抑制活性

进行无细胞酶实验以测定SLx-2119对ROCK1和ROCK2的选择性抑制作用,在非结合表面微孔板上进行反应。使用4mU的人ROCK1和ROCK2磷酸化30 μM合成的ROCK肽底物S6 Long(序列:KEAKEKRQEQIAKRRRLSSLRASTSKSGGSQK),在American Peptide(Sunnyvale,CA)制备得到,在10 mM Mg2+,50 mMTris,pH 7.5, 0.1 mM EGTA和1 mM DTT中加入10 μM ATP(包含33P-ATP),室温下反应。一个单位是每分钟催化 1 nmol磷酸转移到肽所需的激酶量。反应进行45分钟,用3%磷酸终止至终浓度为1%。在磷酸纤维素过滤微孔板上捕获反应,并在真空歧管中用75 mM磷酸和甲醇洗涤。在Perkin-Elmer MicroBeta 1450上测量磷酸化。

细胞实验 [1]:

细胞系

人微血管内皮细胞(HMVEC、CC-2527、Cambrex)

溶解方法

将该化合物溶于DMSO制备20 mM母液。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月

反应条件

含有10 μM或40 μM SLx-2119的3ml培养基,24小时。

实验结果

40 μM的SLx-2119显著降低Tsp-1和CTGF的mRNA水平。

动物实验: [2]

动物模型

C57BL/6小鼠

剂量

100、200 或300 mg/kg;每12小时填喂饲养,施用2天。

实验结果

KD025以前被称为SLx-2119,100和200 mg/kg剂量水平将梗死体积分别减少30%和40%。远端大脑中动脉闭塞(dMCAO)前90分钟给药KD025(200 mg/kg)显著减少灌注缺陷的区域,表明抑制ROCK2可改善急性脑动脉闭塞期间的皮质灌注。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。

References:

[1]. Boerma M, Fu Q, Wang J, et al. Comparative gene expression profiling in three primary human cell lines after treatment with a novel inhibitor of Rho kinase or atorvastatin. Blood Coagul Fibrinolysis, 2008, 19(7): 709-718.

[2]. Lee JH, Zheng Y, von Bornstadt D, et al. Selective ROCK2 Inhibition In Focal Cerebral Ischemia. Ann ClinTranslNeurol, 2014, 1(1): 2-14.

质量控制

化学结构

SLx-2119

相关生物数据

SLx-2119