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^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

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 (t_1/2=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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

305.28

C₁₄H₈FNO₄S

900515-16-4

Room temperature in continental US; may vary elsewhere.

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

In Vitro: 

DMSO : 25 mg/mL (81.89 mM; Need ultrasonic)

*

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

• [1]. Pomel V, 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.

A PI3Kγ lipid kinase assay, based on the neomycin-coated scintillation proximity assay (SPA) bead technology, is performed in 384-well plates using ATP/[γ³³P]ATP and PtdIns. Kinase assays for IC₅₀ value determinations with PI3Kα, PI3Kβ, and PI3Kδ are carried out^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

After 3 h of starvation in serum-free medium, Raw-264 macrophages are pretreated with inhibitors (e.g., AS-252424, 1 nM, 10 nM, 100 nM, 1 μM, 10 μM and 100 μM) or DMSO for 30 min and stimulated for 5 min with 50 nM C5a. PKB/Akt phosphorylation is monitored using phospho-Ser-473 Akt specific antibody and standard ELISA protocols^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Mice^[1]
PI3Kγ knockout (KO) mice are used. Oral administration of AS-252424 at 10 mg/kg is performed in PI3Kγ-deficient mice.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Pomel V, 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.