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GSK429286A

现货
Catalog No.
A5611
选择性ROCK1/ROCK2抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 880.00
现货
5mg
¥ 800.00
现货
25mg
¥ 2,400.00
现货
100mg
¥ 6,000.00
现货

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Background

GSK429286A is a selective inhibitor of ROCK1 and ROCK2 with IC50 value of 14 nM and 63 nM, respectively [1].

Rho-kinase (ROCK) is a member of AGC (protein kinase A, protein kinase G and protein kinase C) family and plays an important role in promoting actin-myosin-mediated contractile force generation [2].

GSK429286A is a potent ROCK inhibitor and has a different activity with the reported ROCK inhibitor Y27632. Using GST method, it is shown that GSK429286A treatment (10 μM) increased MYPT phosphrylation at Thr850 via inhibiting ROCK which mediated this phosphorylation process [3].

In male Sprague-Dawley rat model with spontaneously hypertensive, oral administration of GSK429286A (30 mg/kg) marks reduced mean arterial pressure and the maximum decreased was as 50 mmHg after nearly 2 h treatment [4].

References:
[1].  Nichols, R.J., et al., Substrate specificity and inhibitors of LRRK2, a protein kinase mutated in Parkinson's disease. Biochem J, 2009. 424(1): p. 47-60.
[2].  Shi, J., et al., Distinct roles for ROCK1 and ROCK2 in the regulation of cell detachment. Cell Death Dis, 2013. 4: p. e483.
[3].  Davis, D.A., et al., Increased therapeutic potential of an experimental anti-mitotic inhibitor SB715992 by genistein in PC-3 human prostate cancer cell line. BMC Cancer, 2006. 6: p. 22.
[4].   Goodman, K.B., et al., Development of dihydropyridone indazole amides as selective Rho-kinase inhibitors. J Med Chem, 2007. 50(1): p. 6-9.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt432.37
Cas No.864082-47-3
FormulaC21H16F4N4O2
Solubility≥21.6mg/mL in DMSO, ≥2.73 mg/mL in EtOH with ultrasonic and warming, <3.56 mg/mL in H2O
Chemical NameN-(6-fluoro-1H-indazol-5-yl)-6-methyl-2-oxo-4-[4-(trifluoromethyl)phenyl]-3,4-dihydro-1H-pyridine-5-carboxamide
SDFDownload SDF
Canonical SMILESCC1=C(C(CC(=O)N1)C2=CC=C(C=C2)C(F)(F)F)C(=O)NC3=C(C=C4C(=C3)C=NN4)F
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

细胞实验[1]:

细胞系

MDA-MB-231 (TRPM7 shRNA) 细胞和MCF7 (TRPM7 shRNA)细胞

制备方法

该化合物在DMSO中的溶解度大于10 mM,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

1 μM,24 hours

实验结果

GSK429286A通过抑制Rho激酶,恢复血清诱导的TRPM7敲低细胞的transwell迁移,而不影响MDA-MB-231对照细胞的迁移。同样,抑制Rho激酶拯救了MFC7 TRPM7 shRNA细胞的间隙闭合速度。与MDA-MB-231细胞相比,低浓度的GSK429286A显著增加MCF7对照细胞的间隙闭合速度。

动物实验[2]:

动物模型

雄性Sprague-Dawley大鼠

给药剂量

口服,30 mg/kg

实验结果

GSK429286A具有61%的口服生物利用度,口服给药后,自发性高血压大鼠的平均动脉压显著降低。30 mg/kg口服给药后约2小时,平均动脉压最大减少50 mmHg。

注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

[1] Middelbeek J, Kuipers A J, Henneman L, et al. TRPM7 is required for breast tumor cell metastasis. Cancer research, 2012, 72(16): 4250-4261.

[2] Goodman K B, Cui H, Dowdell S E, et al. Development of dihydropyridone indazole amides as selective Rho-kinase inhibitors. Journal of medicinal chemistry, 2007, 50(1): 6-9.

生物活性

Description GSK429286A是一种选择性ROCK1和ROCK2抑制剂,IC50值分别为14 nM和63 nM。
靶点 ROCK1 ROCK2        
IC50 14 nM 63 nM        

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