CAS NO: | 648449-76-7 |
规格: | ≥98% |
包装 | 价格(元) |
5mg | 电议 |
10mg | 电议 |
25mg | 电议 |
50mg | 电议 |
100mg | 电议 |
250mg | 电议 |
500mg | 电议 |
1g | 电议 |
Molecular Weight (MW) | 285.22 |
Formula | C11H5F2NO4S |
CAS No. | 648449-76-7 |
Storage | -20℃ for 3 years in powder form |
-80℃ for 2 years in solvent | |
Solubility (In vitro) | DMSO: 57 mg/mL (199.84 mM) |
Water:<1 mg/mL | |
Ethanol: 5 mg/mL (17.53 mM) | |
Solubility (In vivo) | 0.5% CMC+0.25% Tween 80: 30mg/mL |
Other info | Synonym: AS604850; AS 604850; AS-604850. Chemical Name: (Z)-5-((2,2-difluorobenzo[d][1,3]dioxol-5-yl)methylene)thiazolidine-2,4-dione InChi Key: SRLVNYDXMUGOFI-YWEYNIOJSA-N InChi Code: InChI=1S/C11H5F2NO4S/c12-11(13)17-6-2-1-5(3-7(6)18-11)4-8-9(15)14-10(16)19-8/h1-4H,(H,14,15,16)/b8-4- SMILES Code: O=C(NC/1=O)SC1=C/C2=CC=C(OC(F)(F)O3)C3=C2 |
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: Hepatocyte cultures are treated with diluent (DMSO), 25 μM TLC, 250 μM TCDC, 50 μM GCDC, or 50 ng/ml Fas for 2-4 hours HepG2-Ntcp and Huh7-Ntcp cells are treated with DMSO, 20 μM TLC, 75 μM TCDC or GCDC, 200 μM etoposide or 200 ng/ml TNFa plus 28 ng/ml actinomycin D for 2-4 hours. The number of apoptotic cells is determined morphologically using fluorescent staining and expressed as % of cells. Apoptosis is confirmed in human cell lines by determination of caspase-3/-7 activity and in rat hepatocytes by detection of the 17 kDa proteolytic cleavage fragment of caspase-3 by immunoblotting; equal protein loading is monitored by immunoblotting for actin. AS-604850 is ATP-competitive PI3Kγ inhibitor with Ki values of 0.18 μM. AS-604850 is isoform selective inhibitor of PI3Kγ with over 30-fold selectivity for PI3Kδ and β, and 18-fold selectivity over PI3Kα. (PI3Kα: IC50 = 4.5 μM, PI3Kγ and β: IC50> 20μM) AS-604850 is capable of inhibiting C5a-mediated PKB phosphorylation in RAW264 mouse macrophages with an IC50 with 10 μM. AS-604850 blocks MCP-1-mediated chemotaxis in Pik3cg +/+ monocytes in a concentration- dependent manner, with an IC50 of 21 mM, but dosn't affect chemotaxis in Pik3cg-/- cells, indicating that AS-604850 acts through PI3Kγ. AS-604850 diminishes glycochenodeoxycholate (GCDC) induced Akt-phosphorylation and apoptosis in rat hepatocytes. AS-604850 diminishes bile salt-induced apoptosis in HepG2 Ntcp and Huh7-Ntcp cells. AS604850 causes a concentration-dependent suppression of chemotactic responses of EoL-1 cells and blood eosinophils to platelet-activating factor (PAF). |
In Vivo | AS-604850 reduces RANTES-induced peritoneal neutrophil recruitment with a ED50 of 42.4 mg/kg. In the thioglycollate-induced peritonitis model, oral administration of 10 mg/kg AS-604850 results in a 31% reduction of neutrophil recruitment |
Animal model | RANTES (0.5 mg/kg in 200 ml saline) or thioglycollate (40 ml/kg) are intraperitoneally injected to C3H mice to induce peritonitis mouse models |
Formulation & Dosage | Dissolved in vehicle (0.5% carboxymethylcellulose/0.25% Tween-20) and adjusted the solution to 10 mL/kg of body weight; 0, 1, 3, 10 or 30 mg/kg for RANTES, 10 mg/kg for thioglycollate; Oral administration |
References | [1] Camps M, et al, Nat Med, 2005, 11(9), 936-943. |