AS-604850

Names

[ Name ]:
AS-604850

[Synonym ]:
5-(2,2-Difluoro-benzo[1,3]dioxol-5-ylmethylene)-thiazolidine-2,4-dione
2,4-Thiazolidinedione, 5-[(2,2-difluoro-1,3-benzodioxol-5-yl)methylene]-, (5Z)-
2,4-Thiazolidinedione, 5-[(2,2-difluoro-1,3-benzodioxol-5-yl)methylene]-, (5E)-
(5Z)-5-[(2,2-Difluoro-1,3-benzodioxol-5-yl)methylene]-1,3-thiazolidine-2,4-dione
(5E)-5-[(2,2-Difluoro-1,3-benzodioxol-5-yl)methylene]-1,3-thiazolidine-2,4-dione

Biological Activity

[Description]:

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].

[Related Catalog]:

Research Areas >> Cancer

Signaling Pathways >> PI3K/Akt/mTOR >> PI3K

[Target]

PI3Kγ:0.25 μM (IC50)

PI3Kγ:0.18 μM (Ki)

PI3Kα:4.5 μM (IC50)

[In Vitro]

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]. Western Blot Analysis[1] 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.

[In Vivo]

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]. Animal Model: Balb/C or C3H mice with human recombinant RANTES or thioglycollate[1] 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.

[References]

[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.

Chemical & Physical Properties

[ Density]:
1.7±0.1 g/cm3

[ Molecular Formula ]:
C₁₁H₅F₂NO₄S

[ Molecular Weight ]:
285.224

[ Exact Mass ]:
284.990723

[ PSA ]:
89.93000

[ LogP ]:
2.63

[ Appearance of Characters ]:
off-white

[ Index of Refraction ]:
1.658

[ Storage condition ]:
2-8°C

[ Water Solubility ]:
DMSO: >10mg/mL

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H317

[ Precautionary Statements ]:
P280

[ Personal Protective Equipment ]:
dust mask type N95 (US);Eyeshields;Faceshields;Gloves

[ Hazard Codes ]:
Xi

[ Risk Phrases ]:
43

[ Safety Phrases ]:
36/37

[ RIDADR ]:
NONH for all modes of transport

Articles

Blockade of PI3Kgamma suppresses joint inflammation and damage in mouse models of rheumatoid arthritis.

Nat. Med. 11 , 936-943, (2005)

Phosphoinositide 3-kinases (PI3K) have long been considered promising drug targets for the treatment of inflammatory and autoimmune disorders as well as cancer and cardiovascular diseases. But the lac...