AS-604850

SKU: orb1300806

Description

AS-604850 is a potent and selective ATP-competitive inhibitor of PI3Kγ, exhibiting an IC50 of 250 nM. It shows 18-fold selectivity over PI3Kα and >80-fold selectivity over PI3Kδ/β. This inhibitor is a valuable research tool for studying PI3Kγ's role in inflammation and immune cell signaling in both cellular and animal models.

Research Area

Signal Transduction

Key Properties

• CAS Number: 648449-76-7
• MW: 285.22
• Purity: 99.84%
• Formula: C₁₁H₅F₂NO₄S
• SMILES: FC1(F)Oc2ccc(\C=C3/SC(=O)NC3=O)cc2O1
• Target: PI3K
• Solubility: Ethanol:5 mg/mL (17.53 mM);H2O:< 1 mg/mL (insoluble or slightly soluble);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (7.01 mM);DMSO:57 mg/mL (199.85 mM)

Bioactivity

• Target IC50:
  PI3Kα:4.5 μM|PI3Kγ:250 nM
• In Vivo:
  AS-604850 reduces RANTES-induced peritoneal neutrophil recruitment with a ED50 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.
• In Vitro:
  AS-604850 is ATP-competitive PI3Kγ inhibitor with Ki values of 0.18 μM. AS-604850 is isoform selective inhibitor of PI3Kγ with over 30-fold selectivity for PI3Kδ and β, and 18-fold selectivity over PI3Kα. (PI3Kα: IC50 = 4.5 μM, PI3Kγ and β: IC50 > 20 μM) AS-604850 is capable of inhibiting C5a-mediated PKB phosphorylation in RAW264 mouse macrophages with an IC50 with 10 μM. AS-604850 blocks MCP-1-mediated chemotaxis in Pik3cg +/+ monocytes in a concentration- dependent manner, with an IC50 of 21 mM, but dosn't affect chemotaxis in Pik3cg-/- cells, indicating that AS-604850 acts through PI3Kγ. AS-604850 diminishes glycochenodeoxycholate (GCDC) induced Akt-phosphorylation and apoptosis in rat hepatocytes. AS-604850 diminishes bile salt-induced apoptosis in HepG2 Ntcp and Huh7-Ntcp cells. AS604850 causes a concentration-dependent suppression of chemotactic responses of EoL-1 cells and blood eosinophils to platelet-activating factor (PAF).
• Cell Research:
  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)

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

inhibit, Inhibitor, AS 604850, AS604850, AS-604850, Phosphoinositide 3-kinase, PI3Kα, PI3K, PI3Kβ, PI3Kγ, PI3Kδ

Compound Identifiers

PubChem CID

5287855