Molecular Weight (MW)

305.28

Formula

C14H8FNO4S

CAS No.

900515-16-4

Storage

-20℃ for 3 years in powder form

-80℃ for 2 years in solvent

Solubility (In vitro)

DMSO: 61 mg/mL (199.81 mM)

Water:<1 mg/mL

Ethanol: <1 mg/mL

Solubility (In vivo)

4% DMSO+50% PEG 300+5% Tween 80+ddH2O: 5mg/mL

Other info

Synonym: AS252424; AS 252424; AS-252424.

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

InChi Key: OYYVWNDMOQPMGE-SDQBBNPISA-N

InChi Code: InChI=1S/C14H8FNO4S/c15-7-1-3-9(10(17)5-7)11-4-2-8(20-11)6-12-13(18)16-14(19)21-12/h1-6,17H,(H,16,18,19)/b12-6-

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

In Vitro

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: 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.

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, ICa and Ca2+ transients in HL-1 cardiomyocytes.

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.

Animal model

Intraperitoneally injecting female C3H mice with thioglycollate (40 ml/kg) to induced a peritonitis mouse model

Formulation & Dosage

Dissolved in vehicle (0.5% carboxymethylcellulose/0.25% Tween-20) and adjusted the solution to 10 mL/kg of body weight.; 10 mg/kg; oral administration。

References

[1] Pomel V, et al, J Med Chem, 2006, 49(13), 3857-3871.; [2] Edling CE, et al, Clin Cancer Res, 2010, 16(20), 4928-4937.