864082-47-3
中文名稱
N-(6-氟-1H-吲唑-5-基)-2-甲基-6-氧代-4-[4-(三氟甲基)苯基]-1,4,5,6-四氫-3-吡啶甲酰胺
英文名稱
N-(6-Fluoro-1H-indazol-5-yl)-2-methyl-6-oxo-4-[4-(trifluoromethyl)phenyl]-1,4,5,6-tetrahydro-3-pyridinecarboxamide
CAS
864082-47-3
分子式
C21H16F4N4O2
分子量
432.37
MOL 文件
864082-47-3.mol
更新日期
2024/12/23 09:09:16
864082-47-3 結(jié)構(gòu)式
基本信息
中文別名
ROCK1和ROCK2抑制劑(GSK429286A)N-(6-氟-1H-吲唑-5-基)-2-甲基-6-氧代-4-[4-(三氟甲基)苯基]-1,4,5,6-四氫-3-吡啶甲酰胺
英文別名
CS-557RHO-15
GSK 429286 A
RHO-15(GSK429286A)
GSK 429286A
GSK-429286A
RHO-15
GSK429286A
GSK-429286A
GSK 429286A
N-(6-Fluoro-1H-indazol-5-yl)-2-methyl-6-oxo-4-(4-(trifluoromethyl)-phenyl)-1,4,5,6-tetrahydrop
N-(6-fluoro-1H-indazol-5-yl)-6-methyl-2-oxo-4-[4-(trifluoromethyl)phenyl]-3,4-dihydro-1H-pyridine-5-carboxamide
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)-1,4,5,6-tetrahydro-2-methyl-6-oxo-4-[4-(trifluoromethyl)phenyl]-3-pyridinecarboxamide
所屬類別
生物化工：ROCK 抑制劑物理化學(xué)性質(zhì)
沸點(diǎn)688.4±55.0 °C(Predicted)
密度1.468
儲(chǔ)存條件2-8°C
儲(chǔ)存條件Sealed in dry,2-8°C
溶解度二甲基亞砜：≥10mg/mL
酸度系數(shù)(pKa)12.10±0.40(Predicted)
形態(tài)粉末
顏色白色至米色
CAS 數(shù)據(jù)庫(kù)864082-47-3
常見(jiàn)問(wèn)題列表
生物活性
GSK429286A是一種選擇性的ROCK1和ROCK2抑制劑，IC50分別為14 nM和63 nM。體外研究
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.體內(nèi)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)是一種選擇性的ROCK1和ROCK2抑制劑，IC50分別為14 nM和63 nM。靶點(diǎn)
| Target | Value |
|
ROCK1
(Cell-free assay) | 14 nM |
|
ROCK2
(Cell-free assay) | 63 nM |
體外研究
GSK429286A輕度抑制RSK 和p70S6K，IC50分別為0.78 μM和1.94 μM。GSK429286A顯著抑制大鼠主動(dòng)脈環(huán)擴(kuò)張，IC50為190 nM。 GSK429286A在1 μM濃度下使ROCK2活性降低20倍，該條件下其它測(cè)定的激酶被顯著抑制的只有MSK1，其活性減低了~5倍。特異性激酶組評(píng)估表明，與廣泛使用的ROCK抑制劑Y-27632相比，GSK429286A是更具有選擇性的ROCK2抑制劑，而即使在30 μM高的劑量下也不顯著抑制LRRK2 (IC50 比對(duì)ROCK2的抑制高500倍)。如同GSK269962A，而不同于sunitinib，10 μM的GSK429286A治療消除基底或G14V-Rho突變體誘導(dǎo)的MYPT在HEK-293細(xì)胞中Thr850上的磷酸化作用，與H-1152和Y-27632具有相似的作用程度，與ROCK介導(dǎo)的磷酸化一致，無(wú)論G14V-Rho 是否存在，GSK429286A均不抑制ERM蛋白磷酸化。
體內(nèi)研究
GSK429286A在雄性Sprague-Dawley大鼠體內(nèi)具有61%的口服生物利用度。GSK429286A以3-30 mg/kg單劑量口服給藥劑量依賴性顯著降低自發(fā)性高血壓大鼠(SHRs)的平均動(dòng)脈壓，30 mg/kg劑量治療大約2小時(shí)后，最大降低50 mmHg。N-(6-氟-1H-吲唑-5-基)-2-甲基-6-氧代-4-[4-(三氟甲基)苯基]-1,4,5,6-四氫-3-吡啶甲酰胺價(jià)格(試劑級(jí))
| 報(bào)價(jià)日期 | 產(chǎn)品編號(hào) | 產(chǎn)品名稱 | CAS號(hào) | 包裝 | 價(jià)格 |
| 2024/11/08 | HY-11000 | N-(6-氟-1H-吲唑-5-基)-2-甲基-6-氧代-4-[4-(三氟甲基)苯基]-1,4,5,6-四氫-3-吡啶甲酰胺 GSK429286A | 864082-47-3 | 5mg | 650元 |
| 2024/11/08 | HY-11000 | N-(6-氟-1H-吲唑-5-基)-2-甲基-6-氧代-4-[4-(三氟甲基)苯基]-1,4,5,6-四氫-3-吡啶甲酰胺 GSK429286A | 864082-47-3 | 10mM * 1mLin DMSO | 720元 |
| 2024/11/08 | HY-11000 | N-(6-氟-1H-吲唑-5-基)-2-甲基-6-氧代-4-[4-(三氟甲基)苯基]-1,4,5,6-四氫-3-吡啶甲酰胺 GSK429286A | 864082-47-3 | 10mg | 1000元 |