AS-252424

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

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

AS-252424 is a potent and selective PI3Kγ inhibitor with an IC50 of 30±10 nM.

AS-252424 also inhibits PI3Kα, PI3Kβ and PI3Kδ with IC50s of 935±150 nM, 20 μM and 20 μM, respectively. 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. In the human monocytic cell line THP-1, MCP-1 binding to the GPCR chemokine receptor CCR2, strongly induces phosphorylation of PKB/Akt, which is effectively inhibited by AS-252424 at IC50 values as low as 0.4 μM. In contrast, induction of PKB/Akt phosphorylation by colony stimulating factor (CSF-1), binding to the growth factor receptor c-fms, is only blocked by AS-252424 at IC50 values as high as 4.7 μM.

Oral administration of AS-252424 in a mouse model of acute peritonitis leads to a significant reduction of leukocyte recruitment. To evaluate the efficacy of AS-252424 to block leukocyte migration in vivo, it is tested in a mouse model of thioglycollate-induced peritonitis. Oral administration of AS-252424 at 10 mg/kg results in moderate reduction of neutrophil recruitment (35%±14%), almost matching the result observed in PI3Kγ-deficient mice. Given the short oral half-life of AS-252424 (t1/2=1 h) and relative high clearance (2.25 L/kg per h), investigations at later time points (24-48 h) to assess macrophage and monoycyte recruitment are not undertaken. The modest pharmacokinetic properties do not appear to be caused by rapid oxidative metabolism (microsomal metabolism after 1 h: 16% (rat), 10% (human)).

AS252424 | AS 252424 | AS-252424

PI3K/Akt/mTOR signaling

PI3K

PI3Kγ| PI3Kα| Casein KiN/Ase 2

Cancer

——

900515-16-4

305.28

C??H?FNO?S

>98% (HPLC)

DMSO:30.5 mg/mL (100 mM)

O=C(NC/1=O)SC1=C/C2=CC=C(C3=CC=C(F)C=C3O)O2

(Z)-5-((5-(4-fluoro-2-hydroxyphenyl)furan-2-yl)methylene)thiazolidine-2,4-dione

(-20℃)

With Ice Pack

≥ 2 years