AS-604850

• CAT Number: R062115
• CAS Number: 648449-76-7
• Molecular Formula: C11H5F2NO4S
• Molecular Weight: 285.22
• Purity: ≥95%
• Synonyms: (5E)-5-[(2,2-difluoro-1,3-benzodioxol-5-yl)methylidene]-1,3-thiazolidine-2,4-dione
• InChI: 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+
• InChIKey: SRLVNYDXMUGOFI-XBXARRHUSA-N
• SMILES: C1=CC2=C(C=C1C=C3C(=O)NC(=O)S3)OC(O2)(F)F

AS-604850 is a potent, selective and ATP-competitive PI3Kγ inhibitor with an IC50 value of 0.25 μM and a Ki value of 0.18 μM. AS-604850 shows isoform selective inhibitor of PI3Kγ with over 30-fold selectivity for PI3Kδ and β, and 18-fold selectivity over PI3Kα, respectively[1].
AS-604850 inhibits C5a-mediated PKB phosphorylation with an IC50 of 10 μM in RAW264 mouse macrophages[1].
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[1].
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[1].
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[1].

Reference

[1]. Camps M, et al. Blockade of PI3Kgamma suppresses joint inflammation and damage in mouse models of rheumatoid arthritis. Nat Med. 2005 Sep;11(9):936-43.
 [Content Brief]