5-[(2,2-二氟-1,3-苯并二恶茂-5-基)亚甲基]噻唑烷-2,4-二酮

生物活性靶点体外研究体内研究 5-[(2,2-二氟-1,3-苯并二恶茂-5-基)亚甲基]噻唑烷-2,4-二酮试剂级价格

CAS号:648449-76-7
英文名:AS 604850
中文名:5-[(2,2-二氟-1,3-苯并二恶茂-5-基)亚甲基]噻唑烷-2,4-二酮
CBNumber:CB5972768
分子式:C11H5F2NO4S
分子量:285.22
MOL File:648449-76-7.mol

5-[(2,2-二氟-1,3-苯并二恶茂-5-基)亚甲基]噻唑烷-2,4-二酮化学性质

密度 :1.71
储存条件 :2-8°C
溶解度 :DMSO: >10mg/mL
形态 :solid
酸度系数(pKa) :7.07±0.20(Predicted)
颜色 :off-white

安全信息

危险品标志 :Xi
危险类别码 :43
安全说明 :36/37
WGK Germany :3

5-[(2,2-二氟-1,3-苯并二恶茂-5-基)亚甲基]噻唑烷-2,4-二酮性质、用途与生产工艺

生物活性 AS-604850 是一种有效的，具有选择性的和 ATP 竞争性的 PI3Kγ 抑制剂，IC50 值为 0.25 μM，Ki 值为 0.18 μM。AS-604850 是 PI3Kγ 的同工型选择性抑制剂，对 PI3Kγ 的选择性是 PI3Kδ/β 的 30 倍以上，是 PI3Kα 的 18 倍以上。

靶点

PI3Kγ

0.25 μM (IC ₅₀ )

PI3Kγ

0.18 μM (Ki)

PI3Kα

4.5 μM (IC ₅₀ )

体外研究

AS-604850 inhibits C5a-mediated PKB phosphorylation with an IC ₅₀ of 10 μM in RAW264 mouse macrophages.
AS-604850 blocks PKB phosphorylation induced by MCP-1 and has little or no effect after stimulation with CSF-1 in in primary monocytes from Pik3cg ^+/+ or Pik3cg ^–/– mice.
AS-604850 (0-30 μM; 15 minutes; primary monocytes from Pik3cg ^+/+ mice) treatment inhibits MCP-1-mediated phosphorylation of PKB and its downstream substrates GSK3α andβ in a concentration-dependent manner. MCP-1-induced phosphorylation of p44/42 ERK (ERK1/2) MAPKs is also reduced, in a concentration dependent manner in primary monocytes from Pik3cg ^+/+ mice.

Western Blot Analysis

Cell Line:	Primary monocytes from Pik3cg ^+/+ mice
Concentration:	0 μM, 1 μM, 3 μM, 10 μM, 30 μM
Incubation Time:	15 minutes
Result:	Inhibited MCP-1-mediated phosphorylation of PKB and its downstream substrates GSK3α andβ in a concentration-dependent manner. MCP-1-induced phosphorylation of p44/42 ERK (ERK1/2) MAPKs was also reduced, in a concentrationdependent manner in primary monocytes from Pik3cg ^+/+ mice.

体内研究

AS-604850 (10-100 mg/kg; oral administration; for 4.5 or 4.25 hours; Balb/C or C3H mice) treatment reduces RANTES-induced peritoneal neutrophil recruitment with an ED ₅₀ value 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:	Balb/C or C3H mice with human recombinant RANTES or thioglycollate
Dosage:	10 mg/kg, 30 mg/kg or 100 mg/kg
Administration:	Oral administration; for 4.5 or 4.25 hours
Result:	Reduced RANTES-induced peritoneal neutrophil recruitment with an ED ₅₀ value of 42.4 mg/kg. In the thioglycollate-induced peritonitis model, resulted in a 31% reduction of neutrophil recruitment.