AS-252424

Cas No.:	900515-16-4
Chemical Name:	(Z)-5-((5-(4-fluoro-2-hydroxyphenyl)furan-2-yl)methylene)thiazolidine-2,4-dione
Synonyms:	AS252424,AS 252424
SMILES:	O=C(NC/1=O)SC1=C/C2=CC=C(C3=CC=C(F)C=C3O)O2
Formula:	C14H8FNO4S
M.Wt:	305.28
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	AS-252424 is a potent and selective PI3Kγ inhibitor with an IC50 of 30±10 nM.
In Vivo:	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))[1].
In Vitro:	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[1].