| Identification | Back Directory | [Name]
GSK-2269557 | [CAS]
1254036-77-5 | [Synonyms]
CS-2463
GSK-2269557
GSK2269557 HCL
GSK-2269557 HCl salt
GSK-2269557 (Nemiralisib HCl)
2-(6-(1H-Indol-4-yl)-1H-indazol-4-yl)-5-((4-isopropylpiperazin-1-yl)methyl)oxazole hydrochloride
6-(1H-indol-4-yl)-4-(5-{[4-(1-methylethyl)-1-piperazinyl]methyl}-1,3-oxazol-2-yl)-1H-indazole hydrochloride
6-(1H-Indol-4-yl)-4-[5-[[4-(1-methylethyl)-1-piperazinyl]methyl]-2-oxazolyl]-1H-indazole hydrochloride (1:1) | [Molecular Formula]
C26H29ClN6O | [MDL Number]
MFCD27956958 | [MOL File]
1254036-77-5.mol | [Molecular Weight]
477.001 |
| Chemical Properties | Back Directory | [storage temp. ]
Store at -20°C | [solubility ]
≤0.2mg/ml in ethanol;20mg/ml in DMSO;14mg/ml in dimethyl formamide | [form ]
crystalline solid | [Appearance]
white solid |
| Hazard Information | Back Directory | [Uses]
Nemiralisib hydrochloride (GSK2269557) is a potent and highly selective PI3Kδ inhibitor with a pKi of 9.9. | [Biological Activity]
pki : 9.9gsk2269557 is an inhibitor of pi3kδ.phosphoinositide 3-kinase delta (pi3kδ), a lipid kinase belonging to the class 1 pi3k family, catalyzes the phosphorylation of phosphatidylinositol-4,5-bisphosphate to produce the critical signalling molecule phosphatidylinositol-3,4,5-triphosphate and then triggers various downstream biological events that ultimately regulate cell proliferation, growth, differentiation, chemotaxis and survival. | [in vitro]
in the screening study, gsk2269557 met the original potency goal in the pbmc assay (pic50 >9) and showed exquisite selectivity against the pi3k isoforms in a modified htrf assay. moreover, gsk2269557 could induce concentration-dependent increases in qt interval and tpe at 0.3 and 1 μm and an increase in qrs at 1 μm, however, no treatment-related tdp arrhythmias were seen [1]. | [in vivo]
in a disease relevant brown norway rat acute ova model of th2 driven lung inflammation, gsk2269557 was found to be albe to protect against eosinophil recruitment with an ed50 of 67 μg/kg. the activity of gsk2269557 was also assessed using other endpoints, leukocyte recruitment to the lung (neutrophils, macrophages, cd4 and cd8 t-lymphocytes at 48 hours) and th2 cytokines such as il-13. it was found that gsk2269557 could reduce recruitment of all leukocyte subpopulations and il-13 in the lungs in a dose-dependent manner [1]. | [IC 50]
PI3Kδ: 9.9 (pKi); PI3Kγ: 5.2 (pIC50); PI3Kα: 5.3 (pIC50); PI3Kβ: 5.8 (pIC50) | [References]
[1] down, k. ,amour, a.,baldwin, i.r., et al. optimization of novel indazoles as highly potent and selective inhibitors of phosphoinositide 3-kinase δ for the treatment of respiratory disease. j. med. chem. 58(18), 7381-7399 (2015).
[2] robert wilson, anthony cahn, amanda deans, iain mcsherry, curtis rambaran, ana sousa, darren wilbraham. safety, tolerability and pharmacokinetics (pk) of single and repeat nebulised doses of a novel phosphoinositide 3-kinase δ inhibitor (pi3kδ), gsk2269557, administered to healthy male subjects in a phase i study. european respiratory journal 2013 42: p729. |
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| Company Name: |
SPIRO PHARMA
|
| Tel: |
|
| Website: |
www.spiropharma.com.cn |
| Company Name: |
Cckinase, Inc.
|
| Tel: |
+1 (732)236-3202 |
| Website: |
www.cckinase.com |
|