生物活性

• 靶点

  PI3Kα IC50:60nM

  PI3Kβ IC50:270nM

  PI3Kδ IC50:300nM

  PI3Kγ IC50:8nM

• 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. 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. 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. 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.

• 动物研究
  剂量	Mice: 30 mg/kg[3] (i.p.); 30 mg/kg[4] (p.o.), 50 mg/kg[5] (p.o.)
  给药途径	i.p., p.o.