中文名称:

N-(6-氟-1H-吲唑-5-基)-2-甲基-6-氧代-4-[4-(三氟甲基)苯基]-1,4,5,6-四氢-3-吡啶甲酰胺

中文同义词:

N-(6-氟-1H-吲唑-5-基)-2-甲基-6-氧代-4-[4-(三氟甲基)苯基]-1,4,5,6-四氢-3-吡啶甲酰胺;ROCK1和ROCK2抑制剂(GSK429286A)

英文名称:

N-(6-Fluoro-1H-indazol-5-yl)-2-methyl-6-oxo-4-[4-(trifluoromethyl)phenyl]-1,4,5,6-tetrahydro-3-pyridinecarboxamide

英文同义词:

RHO-15(GSK429286A);GSK 429286 A;RHO-15;N-(6-fluoro-1H-indazol-5-yl)-2-methyl-6-oxo-4-(4-(trifluoromethyl)phenyl)-1,4,5,6-tetrahydropyridine-3-carboxamide;GSK 429286 A N-(6-Fluoro-1H-indazol-5-yl)-2-methyl-6-oxo-4-[4-(trifluoromethyl)phenyl]-1,4,5,6-tetrahydro-3-pyridinecarboxamide;N-(6-Fluoro-1H-indazol-5-yl)-2-methyl-6-oxo-4-[4-(trifluoromethyl)phenyl]-1,4,5,6-tetrahydro-3-pyridinecarboxamide GSK 429286 A;N-(6-Fluoro-1H-indazol-5-yl)-1,4,5,6-tetrahydro-2-methyl-6-oxo-4-[4-(trifluoromethyl)phenyl]-3-pyridinecarboxamide;N-(6-Fluoro-1H-indazol-5-yl)-2-methyl-6-oxo-4-[4-(trifluoromethyl)phenyl]-1,4,5,6-tetrahydro-3-pyridinecarboxamide

CAS号:

864082-47-3

分子式:

C21H16F4N4O2

分子量:

432.37

EINECS号:

相关类别:

细胞生物学试剂;小分子抑制剂，天然产物;细胞周期;小分子抑制剂;Inhibitors

Mol文件:

864082-47-3.mol

沸点 

688.4±55.0 °C(Predicted)

密度 

1.468

储存条件 

Sealed in dry,2-8°C

溶解度 

DMSO: ≥10mg/mL

形态

powder

酸度系数(pKa)

12.10±0.40(Predicted)

颜色

white to beige

CAS 数据库

864082-47-3

生物活性

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

体外研究

GSK429286A slightly inhibits RSK and p70S6K with IC50 of 0.78 μM and 1.94 μM, respectively. GSK429286A significantly inhibits rat aortic ring dilation with IC50 of 190 nM. GSK429286A at 1 μM reduces ROCK2 activity over 20-fold, under conditions in which the only other kinase tested that is significantly inhibited is MSK1 whose activity is reduced ~5-fold. GSK429286A is a more selective ROCK2 inhibitor than the widely utilized ROCK inhibitor Y-27632 as assessed on kinase-specificity panel, and does not significantly inhibit LRRK2 even at doses as high as 30 μM (500-fold higher than IC50 of inhibition of ROCK2). Like GSK269962A but not sunitinib, GSK429286A treatment at 10 μM ablates basal or G14V-Rho mutant induced phosphorylation of MYPT at Thr850 in HEK-293 cells to a similar extent as H-1152 and Y-27632, consistent with ROCK mediating this phosphorylation, whereas GSK429286A does not inhibit ERM protein phosphorylation either in the presence or absence of G14V-Rho.

体内研究

GSK429286A has 61% oral bioavailability in male Sprague-Dawley rats. Oral administration of GSK429286A at single doses of 3-30 mg/kg dramatically reduces mean arterial pressure in the spontaneously hypertensive rats (SHRs) in a dose-dependent manner, with a maximum decrease of 50 mmHg after approximately 2 hours treatment at dose of 30 mg/kg.

特征

More selective than Y-27632.

生物活性

GSK429286A (RHO-15)是一种选择性的ROCK1和ROCK2抑制剂，IC50分别为14 nM和63 nM。

靶点

Target Value ROCK1 (Cell-free assay) 14 nM ROCK2 (Cell-free assay) 63 nM

Target

Value

ROCK1 (Cell-free assay)

14 nM

ROCK2 (Cell-free assay)

63 nM

体外研究

GSK429286A轻度抑制RSK 和p70S6K，IC50分别为0.78 μM和1.94 μM。GSK429286A显著抑制大鼠主动脉环扩张，IC50为190 nM。 GSK429286A在1 μM浓度下使ROCK2活性降低20倍，该条件下其它测定的激酶被显著抑制的只有MSK1，其活性减低了~5倍。特异性激酶组评估表明，与广泛使用的ROCK抑制剂Y-27632相比，GSK429286A是更具有选择性的ROCK2抑制剂，而即使在30 μM高的剂量下也不显著抑制LRRK2 (IC50 比对ROCK2的抑制高500倍)。如同GSK269962A，而不同于sunitinib，10 μM的GSK429286A治疗消除基底或G14V-Rho突变体诱导的MYPT在HEK-293细胞中Thr850上的磷酸化作用，与H-1152和Y-27632具有相似的作用程度，与ROCK介导的磷酸化一致，无论G14V-Rho 是否存在，GSK429286A均不抑制ERM蛋白磷酸化。

体内研究

GSK429286A在雄性Sprague-Dawley大鼠体内具有61%的口服生物利用度。GSK429286A以3-30 mg/kg单剂量口服给药剂量依赖性显著降低自发性高血压大鼠(SHRs)的平均动脉压，30 mg/kg剂量治疗大约2小时后，最大降低50 mmHg。

危险品标志 

T

危险类别码 

25

安全说明 

45

危险品运输编号 

UN 2811 6.1 / PGIII

WGK Germany 

3