5-[[5-(4-氟-2-羟基苯基)-2-呋喃基]亚甲基]-2,4-噻唑烷二酮

AS-252424是一种新型，有效的PI3Kγ抑制剂，IC50为30 nM，作用于PI3Kγ比作用于PI3Kα选择性高30倍，对PI3Kδ/β具有低的抑制活性。 AS-252424 is a furan-2-ylmethylene thiazolidinedione as a selective ATP-competitive PI3Kγ inhibitor with IC50 with 33 nM. AS-252424 shows reduced potency on PI3Kα with an IC50 with 935 nM. When screening against 80 different Ser/Thr and Tyr kinases, AS-252424 doesn't show significant inhibit towards any of them at 10 μM except for CK2. AS-252424 inhibits C5a-mediated PKB/Akt phosphorylation in a concentration- dependent manner with submicromolar or low-micromolar IC50 value. AS-252424 inhibits MCP-1-mediated chemotaxis in wild-type primary monocytes in a concentration-dependent manner with an IC50 value of 52 μM, as well as in the monocytic cell line THP-1 with an IC50 value of 53 μM. AS252424 specifically blocks proliferation in the pancreatic cancer cell lines HPAF and Capan1, as assessed by cell counting. A recent research indicates 100 nM of AS-252424 significantly reduces [Ca²⁺]i, I_Ca and Ca²⁺ transients in HL-1 cardiomyocytes. Oral administration of AS-252424 at 10 mg/kg results in moderate reduction of neutrophil recruitment (35%), almost matching the result observed in PI3Kγ-deficient mice.

PI3Kα 935 nM (IC 50 )

PI3Kγ 30 nM (IC 50 )

PI3Kδ 20 μM (IC 50 )

PI3Kβ 20 μM (IC 50 )