GSK2593074A

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

GSK2593074A (GSK'074, GSK-2593074A) 是新型有效的选择性 RIP1/RIP3 激酶双重抑制剂。

GSK2593074A (GSK'074, GSK-2593074A) is novel potent, selective RIP1/RIP3 kinase dual inhibitor, directly binds to RIP1 and RIP3 with Kd of 130 and 12 nM, respectively; potently inhibits necroptosis in various cell types (IC50=3 nM both in MOVAS and L929 cells), blocks necroptosis signaling pathway; inhibits RIP3-dependent RIP1-independent necroptosis and inflammation, but does not induce apoptosis; attenuates cell death and inflammation in calcium phosphate injured aortae.

GSK2593074A (GSK’074; 0.01, 0.1, 1, 10, and 100 nM; 6?hours for MOVAS cells; 3 hours for L929 cells) completely rescues cells from necroptosis under different stimuli in both human and murine cells at IC50~3?nM. In multiple cell types including mouse SMCs, fibroblasts (L929), bone marrow derived macrophages (BMDM), and human colon epithelial cells (HT29), GSK2593074A inhibits necroptosis with an IC50 of ~3?nM. Cell Viability Assay Cell Line:Mouse smooth muscle cell line MOVAS; Mouse fibroblast cell line L929Concentration:0.01, 0.1, 1, 10, and 100 nM Incubation Time:6?hours for MOVAS cells; 3 hours for L929 cells Result:Inhibited MOVAS and L929 cells with the IC50 of 3 nM.

GSK2593074A (GSK’074; 0.93?mg/kg/day; i.p. injection; 14 or 28 days) is administrated to Apoe-/- mice immediately following pump implantation. Compared to the DMSO group, GSK2593074A-treated mice show significantly alleviated aneurysm formation, reflected by a much smaller aortic dilatation (DMSO 85.39±15.76% vs GSK2593074A 36.28±5.76%; P<0.05) as well as a reduced abdominal aortic aneurysm (AAA) incidence (from 83.3 to 16.7%). GSK2593074A significantly decreases the extent of aortic expansion (DMSO 66.06±9.17% vs GSK2593074A 27.36±8.25%; P<0.05) . Animal Model:Apoe-/- female mice (9-10 months)Dosage:0.93?mg/kg/day; 200?μL Administration:Daily i.p. injection; 14 or 28 days Result:Inhibited aneurysm formation in mouse models of aneurysms.

GSK'074 | GSK-2593074A

Apoptosis

RIP kinase

RIP kinase

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1337531-06-2

465.575

C27H23N5OS

>98% (HPLC)

In Vitro:?DMSO : 41.67 mg/mL (89.50 mM)

CN1N=CC(C2=CN=C(N)C3=C2SC=C3C4=CC5=C(N(C(CC6=CC=CC=C6)=O)CC5)C=C4)=C1

1-(5-(4-amino-7-(1-methyl-1H-pyrazol-4-yl)thieno[3,2-c]pyridin-3-yl)indolin-1-yl)-2-phenylethan-1-one

(-20℃)

With Ice Pack

≥ 2 years