AS-605240

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Chemical Structure| 648450-29-7 同义名 : -
CAS号 : 648450-29-7
货号 : A108127
分子式 : C12H7N3O2S
纯度 : 98%
分子量 : 257.268
MDL号 : MFCD11114066
存储条件：

Pure form Sealed in dry,2-8°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 3 mg/mL(11.66 mM)，配合低频超声，并水浴加热至45℃助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO

H2O: 2.5 mg/mL(9.72 mM)，配合低频超声，水浴加热至45℃，并调节pH至10
动物实验配方：

PO 0.5% CMC-Na 80 mg/mL clear

生物活性
靶点

  • p110γ

    PI3Kγ, IC50:8 nM

  • p110β

    PI3Kβ, IC50:270 nM

  • p110α

    PI3Kα, IC50:60 nM

  • p110δ

    PI3Kδ, IC50:300 nM
描述 The phosphoinositide 3-kinases (PI3Ks) control a number of essential intracellular signaling pathways involved in the cell life cycle, and play a critical role in the cardiovascular system. The PI3K family is divided into three classes, with class I divided into subclass IA and IB. PI3K-α, -β, and -δ isoforms belong to class IA and are primarily activated by receptor tyrosine kinases, whereas PI3K-γ isoform, which belongs to class IB, are facilitated by G-protein-coupled receptors (GPCRs). PI3K-γ is a key regulator of inflammatory responses and cardiovascular homeostasis. PI3Kγ is also a mediator in G-protein coupled receptor signaling and therefore is involved in the directed migration of neutrophils and macrophages in response to chemokines[3]. AS-605240 is a specific PI3Kγ inhibitor with IC50s 8 nM, 68 nM, 312 nM, and 386 nM for PI3Kγ, PI3Kα, PI3Kβ and PI3Kδ, respectively. AS-605240 can reduce the phosphorylation level of its downstream Akt[3]. In a vitro study, treatment with 10 μM AS-605240 for 0, 2, 5 or 10 minutes blocked all Akt phosphorylation in T-ALL cell lines including 1156, 1713, C6, and C7 cell lines with high RasGRP1 expression[4]. Administration of AS605240 at a dose of 10 mg/kg for 24h to LPS-treated mice reduced some patho-physiological characteristics of SIMD and reduced TNF-α, IL-6, cTnI and H-FABP production[3].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
RAW264.7 cells Function assay Inhibition of MCP1-induced chemotaxis in mouse RAW264.7 cells, IC50=5.31 μM 19904929
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

3.89mL

0.78mL

0.39mL

19.43mL

3.89mL

1.94mL

38.87mL

7.77mL

3.89mL
参考文献

[1]Kim JI, Lee HR, et al. PI3Kγ is required for NMDA receptor-dependent long-term depression and behavioral flexibility. Nat Neurosci. 2011 Oct 23;14(11):1447-54.

[2]Camps M, Ruckle T, et al. Blockade of PI3Kgamma suppresses joint inflammation and damage in mouse models of rheumatoid arthritis. Nat Med. 2005 Sep;11(9):936-43. Epub 2005 Aug 28.

[3]Fan TT, Feng XY, Yang YZ, Gao F, Liu Q. Downregulation of PI3K-γ in a mouse model of sepsis-induced myocardial dysfunction. Cytokine. 2017 Aug;96:208-216. doi: 10.1016/j.cyto.2017.04.018. Epub 2017 Apr 28. PMID: 28458167.

[4]Ksionda O, Mues M, Wandler AM, Donker L, Tenhagen M, Jun J, Ducker GS, Matlawska-Wasowska K, Shannon K, Shokat KM, Roose JP. Comprehensive analysis of T cell leukemia signals reveals heterogeneity in the PI3 kinase-Akt pathway and limitations of PI3 kinase inhibitors as monotherapy. PLoS One. 2018 May 25;13(5):e0193849. doi: 10.1371/journal.pone.0193849. PMID: 29799846; PMCID: PMC5969748.