AS-252424

 

Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw

Biological Activity

Description	AS-252424 is a novel, potent PI3Kγ inhibitor with IC50 of 30 nM with 30-fold selectivity for PI3Kγ than PI3Kα, and low inhibitory activity towards PI3Kδ/β.
Targets	PI3Kγ	CK2 (casein kinase 2)	PI3Kα
IC50	33 nM	20 nM	935 nM [1]
In vitro	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 doesnot 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. [1] AS252424 specifically blocks proliferation in the pancreatic cancer cell lines HPAF and Capan1, as assessed by cell counting. [2] A recent research indicates 100 nM of AS-252424 significantly reduces [Ca2+]i, ICa and Ca2+ transients in HL-1 cardiomyocytes. [3]
In vivo	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. [1]
Features

Protocol(Only for Reference)

Kinase Assay: ^[1]

In vitro PI3Kγ Kinase Assay

Human PI3Kγ (100 ng) is incubated at RT with kinase buffer (10 mM MgCl2, 1 mM β-glycerophosphate, 1 mM DTT, 0.1 mM Na3VO4, 0.1% Na Cholate and 15 M ATP/100 nCi γ[33]ATP, final concentrations) and lipid vesicles containing 18 M PtdIns and 250 M of PtdSer (final concentrations), in the presence of AS-252424 or DMSO. Kinase reaction is stopped by adding 250 g of Neomycin-coated Scintillation Proximity Assay (SPA) beads and preceded.

Cell Assay: ^[1]

Cell lines	Raw-264 macrophage
Concentrations	0.01 nM to 0.1 μM
Incubation Time	5 minutes
Method	After 3 hours of starvation in serum-free medium, Raw-264 macrophages are pretreated with AS-252424 or DMSO for 30 minutes and stimulated for 5 minutes with 50 nM C5a. PKB/Akt phosphorylation is monitored using phospho-Ser-473 Akt specific antibody and standard ELISA protocols.

Animal Study: ^[1]

Animal Models	Intraperitoneally injecting female C3H mice with thioglycollate (40 ml/kg) to induced a peritonitis mouse model
Dosages	10 mg/kg
Administration	Oral administration 15 minutes before injection of thioglycollate
Solubility	0.5% CMC/0.25% Tween 80, 30 mg/mL

1

References

Chemical Information

Download AS-252424 SDF

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

Preparing Stock Solutions

Stock Solution (1ml DMSO)	1mM	10mM	20mM	30mM
Mass(mg)	0.30528	3.0528	6.1056	9.1584

Customer Reviews (1)

Click to enlarge	Rating
	Source	Dr. Zhang of Tianjin Medical University. AS-252424 purchased from Selleck
	Method	Western blot
	Cell Lines	A549 cells
	Concentrations	0-10 μM
	Incubation Time	3 h
	Results	AS-252424 treatment resulted in a reduction of AKT phosphorylation.

Product Citations (3)

• 
  

  Phosphoinositide 3 kinase inhibition restores neutrophil accuracy in the elderly: towards targeted treatments for immunesenescence. [Sapey E, et al. Blood 2014;123(2):239-51]

  
  PubMed: 24191150


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  Pharmacological profiling of phosphoinositide-3-kinase inhibitors as mitigators of ionizing radiation-induced cell death. [Lazo JS, et al. J Pharmacol Exp Ther 2013;347(3):669-80]

  
  PubMed: 24068833


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  Selective CDK9 inhibition overcomes TRAIL resistance by concomitant suppression of cFlip and Mcl-1. [Lemke J ,et al. Cell Death Differ 2013;10.1038/cdd.2013.179]

  
  PubMed: 24362439