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AS-252424
本产品不向个人销售，仅用作科学研究，不用于任何人体实验及非科研性质的动物实验。
AS-252424图片
包装与价格：
包装价格(元)
10mM (in 1mL DMSO)电议
5mg电议
10mg电议

产品介绍
AS-252424 是一种有效的选择性 PI3Kγ 抑制剂，IC50 为 30±10 nM。

Kinase experiment:

A PI3Kγ lipid kinase assay, based on the neomycin-coated scintillation proximity assay (SPA) bead technology, is performed in 384-well plates using ATP/[γ33P]ATP and PtdIns. Kinase assays for IC50 value determinations with PI3Kα, PI3Kβ, and PI3Kδ are carried out[1].

Cell experiment:

After 3 h of starvation in serum-free medium, Raw-264 macrophages are pretreated with inhibitors (e.g., AS-252424, 1 nM, 10 nM, 100 nM, 1 μM, 10 μM and 100 μM) or DMSO for 30 min and stimulated for 5 min with 50 nM C5a. PKB/Akt phosphorylation is monitored using phospho-Ser-473 Akt specific antibody and standard ELISA protocols[1].

Animal experiment:

Mice[1]PI3Kγ knockout (KO) mice are used. Oral administration of AS-252424 at 10 mg/kg is performed in PI3Kγ-deficient mice.

产品描述

AS-252424 is a potent, selective and novel small-molecule PI3Kγ inhibitor (IC50= 30 nM)

PI3K (phosphatidylinositol-4,5-bisphosphate 3-kinase) is a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which in turn are involved in cancer. It plays a key role in PI3K/Akt/mTOR pathway.

In THP-1 (human monocytic cell line), AS-252424 inhibited the phosphorylation of PKB/Akt due to MCP1 binding to the GPCR receptor CCR2 at lowest IC50 values of 0.4 μM. In primary monocytes and monocytic wild-type cell line THP-1, AS-252424 inhibited MCP-1-mediated chemotaxis in a concentration-dependent manner (IC50 value= 52 μM and 53 μM, respectively). [1] In Capan 1 and HPAF (pancreatic cancer cell lines), AS52424 specifically inhibited the cell proliferation. [2]

In a mouse model of thioglycollate-induced peritonitis, oral administration of AS-252424 at 10 mg/kg led to moderate reduction of neutrophil recruitment (35% ±14%). [1]

References:
1. Pomel V, Klicic J, Covini D et al. Furan-2-ylmethylene thiazolidinediones as novel, potent, and selective inhibitors of phosphoinositide 3-kinase gamma. J Med Chem. 2006 Jun 29;49(13):3857-71.
2.  Edling CE, Selvaggi F, Buus R et al. Key role of phosphoinositide 3-kinase class IB in pancreatic cancer. Clin Cancer Res. 2010 Oct 15;16(20):4928-37.