5-[[5-(4-Fluoro-2-hydroxyphenyl)-2-furanyl]methylene]-2,4-thiazolidinedione

Uses

AS-252424 is a novel, potent, and selective phosphoinositide 3-kinase gamma (PI3Kγ) inhibitor. It is also an inhibitor of Casein kinase and PI3K p110α.

Biological Activity

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]

Biochem/physiol Actions

AS-252424 is a potent and selective phosphoinositide 3-kinase PI3Kγ inhibitor with IC50 = 30 nM in a mouse model.

in vivo

IC 50

PI3Kγ: 30 nM (IC₅₀); PI3Kα: 935 nM (IC₅₀); PI3Kδ: 20 μM (IC₅₀); PI3Kβ: 20 μM (IC₅₀)

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.