GSK2269557
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
pKi : 9.9
GSK2269557 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].
Clinical trial: GSK2269557 was investigated in a double blind and placebo controlled trial in healthy males and smokers. It was found that GSK2269557 was well tolerated in healthy males. There was a low incidence of AE’s and the plasma PK was well defined confirming high levels of drug within the lung compared to plasma [2].
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.
Physical Appearance | A crystalline solid |
Storage | Store at -20°C |
M.Wt | 477 |
Cas No. | 1254036-77-5 |
Formula | C26H28N6O·HCl |
Solubility | ≤0.2mg/ml in ethanol;20mg/ml in DMSO;14mg/ml in dimethyl formamide |
Chemical Name | 6-(1H-indol-4-yl)-4-[5-[[4-(1-methylethyl)-1-piperazinyl]methyl]-2-oxazolyl]-1H-indazole, monohydrochloride |
SDF | Download SDF |
Canonical SMILES | CC(C)N(CC1)CCN1CC2=CN=C(C3=C(C=NN4)C4=CC(C5=CC=CC6=C5C=CN6)=C3)O2 |
运输条件 | 蓝冰运输或根据您的需求运输。 |
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