| Description | AS-604850 is a specific and ATP-competitive PI3Kγ inhibitor (IC50: 250 nM), 18-fold more selective for PI3Kγ than PI3Kα, and over 80-fold selectivity for PI3Kγ than PI3Kδ/β. |
| In vitro | AS-604850是一种与ATP竞争的PI3Kγ抑制剂，其Ki值为0.18μM。该化合物是PI3Kγ的同型选择性抑制剂，对PI3Kδ和β具有超过30倍的选择性，对PI3Kα则具有18倍的选择性。（PI3Kα: IC50 = 4.5μM, PI3Kγ和β: IC50 > 20μM）AS-604850能够抑制RAW264小鼠巨噬细胞中C5a介导的PKB磷酸化，其IC50为10μM。此外，AS-604850以浓度依赖性方式阻断Pik3cg+/+单核细胞中MCP-1介导的趋化作用，IC50为21mM，但不影响Pik3cg-/-细胞的趋化作用，表明AS-604850通过PI3Kγ发挥作用。[1] AS-604850减少了大鼠肝细胞中甘胆酸诱导的Akt磷酸化和凋亡。此外，AS-604850减轻了HepG2 Ntcp和Huh7-Ntcp细胞中胆盐诱导的凋亡。[2] AS604850能够浓度依赖地抑制EoL-1细胞和血嗜酸性粒细胞对血小板激活因子（PAF）的趋化反应。[3] |
| In vivo | AS-604850通过口服给药，在ED50为42.4 mg/kg的条件下，能有效降低RANTES引起的腹膜中性粒细胞的招募。在硫代乙酸盐引起的腹膜炎模型中，10 mg/kg剂量的AS-604850能使中性粒细胞招募减少31%。[1] |
| Cell experiments | 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.(Only for Reference) |
| Target activity | PI3Kγ:250 nM |
| Synonyms | 5-[(2,2-二氟-1,3-苯并二恶茂-5-基)亚甲基]噻唑烷-2,4-二酮 |
| molecular weight | 285.22 |
| Molecular formula | C11H5F2NO4S |
| CAS | 648449-76-7 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | Ethanol: 5 mg/mL (17.53 mM) H2O: < 1 mg/mL (insoluble or slightly soluble) DMSO: 57 mg/mL (199.84 mM) |
| References | 1. Camps M, et al, Nat Med, 2005, 11(9), 936-943. 2. Hohenester S, et al, J Hepatol, 2010, 53(5), 918-926. 3. Hasan AM, et al, Int Immunopharmacol, 2010, 10(9), 12017-1021. |
| Citations | 1. Lu C, Liu J, Escames G, et al.PIK3CG Regulates NLRP3/GSDMD-Mediated Pyroptosis in Septic Myocardial Injury.Inflammation.2023: 1-17. |