AS-604850

Research use only, not for human use.

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.

AS-604850 is a selective PI3Kγ inhibitor, which significantly reduced the number of infiltrated leukocytes in the CNS and ameliorated the clinical symptoms of EAE mice. Treatment with this PI3Kγ inhibitor enhanced myelination and axon number in the spinal cord of EAE mice. PI3Kγ contributes to development of autoimmune CNS inflammation and that PI3Kγ blockade may provide a great potential for treating patients with MS.

AS-604850 inhibits C5a-mediated PKB phosphorylation with an IC50 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 concentration dependent manner in primary monocytes from Pik3cg+/+ mice.

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 ED50 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 ED50 value of 42.4 mg/kg. In the thioglycollate-induced peritonitis model, resulted in a 31% reduction of neutrophil recruitment.

AS604850 | AS 604850 | AS-604850

Others

Other Targets

PI3Kα| PI3Kβ| PI3Kγ| PI3Kδ

Inflammation/Immunology

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648449-76-7

285.22

C11H5F2NO4S

>98% (HPLC)

In Vitro:?DMSO : 250 mg/mL (876.52 mM)

c1cc2c(cc1/C=C\1/C(=O)NC(=O)S1)OC(O2)(F)F

(Z)-5-((2,2-difluorobenzo[d][1,3]dioxol-5-yl)methylene)thiazolidine-2,4-dione

(-20℃)

With Ice Pack

≥ 2 years