product name AS-252424
Description: AS-252424 is a novel, potent PI3Kγ inhibitor with IC50 of 30 nM in a cell-free assay with 30-fold selectivity for PI3Kγ than PI3Kα, and low inhibitory activity towards PI3Kδ/β. In THP-1 (human monocytic cell line), AS-252424 inhibited the phosphorylation of PKB/Akt due to MCP1 binding to the GPCR receptor CCR2 at lowest IC50 values of 0.4 μM. In primary monocytes and monocytic wild-type cell line THP-1, AS-252424 inhibited MCP-1-mediated chemotaxis in a concentration-dependent manner (IC50 value= 52 μM and 53 μM, respectively). In Capan 1 and HPAF (pancreatic cancer cell lines), AS52424 specifically inhibited the cell proliferation.
References: J Med Chem. 2006 Jun 29;49(13):3857-71; Clin Cancer Res. 2010 Oct 15;16(20):4928-37.
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
Chemical Name
(5Z)-5-[[5-(4-fluoro-2-hydroxyphenyl)furan-2-yl]methylidene]-1,3-thiazolidine-2,4-dione
other peoduct :
| 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 doesnt 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. |
