AS-605240

SKU: orb1224353

Description

AS-605240 (AS605240) is a potent, selective, ATP-competitive, orally active PI3Kγ inhibitor with IC50 of 8 nM; displays 30-fold selectivity for PI3Kδ、β, 7.5-fold selectivity over PI3Kα; inhibits C5a-mediated PKB phosphorylation in RAW264 mouse macrophages (IC50=90 nM); reduces neutrophil chemotaxis in vivo and suppresses joint inflammation and damage in mouse models of RA.

Key Properties

• CAS Number: 648450-29-7
• MW: 257.2679
• Purity: >98% (HPLC)
• Formula: C₁₂H₇N₃O₂S
• SMILES: O=C(NC/1=O)SC1=C\C2=CC=C3N=CC=NC3=C2
• Target: PI3K
• Solubility: DMSO: 5.8 mg/mL (Need warming)

Bioactivity

• In Vivo:
  AS-605240 (30 mg/kg BW, per os, every 12 h) markedly decreases FoxM1 expression in mouse lungs and fails to restore vascular integrity. AS-605240 reduces RANTES-induced peritoneal neutrophil recruitment, with ED50 of 9.1 mg/kg. In the CCL5 model, AS-605240 shows an ED50 value of 10 mg/kg, in correlation with the percentage of reduction of neutrophil recruitment observed in Pik3cg-/-mice. AS-605240 (50 mg/kg, p.o.) substantially reduces clinical and histological signs of joint inflammation to a similar extent to that of Pik3cg-/-mice. AS605240 (30 mg/kg, i.p.) suppresses intracellular PAkt in splenocytes of NOD mice and delays diabetes onset. AS605240 also prevents autoimmune diabetes in prediabetic NOD mice, and suppresses autoreactive T cells while increasing Tregs in NOD mice. AS605240 (30 mg/kg, i.p.) reverses hyperglycemia in newly hyperglycemic NOD mice, reverses hyperglycemia in early diabetic NOD mice through Tregs and suppresses T-cell infiltration in pancreatic islets while increasing Tregs. AS605240 (25, 50 mg/kg) markedly reduces total cell count and numbers of macrophages, neutrophils and lymphocytes in rats. AS605240 significantly reduces the levels of TNF-α and IL-1β in BALF to 132.7±11.2 pg/mL and 49.2±11.3 pg/mL in 25 mg/kg AS605240 + BLM group and 131.3±10.7 and 49.6±8.8 pg/mL in 50 mg/kg AS605240 + BLM group, respectively. AS605240 inhibits prefibrotic cytokines production in bleomycin-induced pulmonary fibrosis. AS605240 inhibits phosphorylation of Akt of inflammatory cells in bleomycin-induced pulmonary fibrosis model.
• In Vitro:
  AS-605240 is an isoform-selective inhibitor of PI3Kγ with over 30-fold selectivity for PI3Kδ and β, and 18- and 7.5-fold selectivity over PI3Kα, respectively. AS-605240 shows an inhibitory effect on C5a-mediated PKB phosphorylation in RAW264 mouse macrophages with an IC50 of 0.09 μM. AS-605240 blocks PKB phosphorylation induced by MCP-1 and has little or no effect after stimulation with CSF-1. AS-605240 inhibits MCP-1-mediated phosphorylation of PKB and its downstream substrates GSK3α and β in a concentration-dependent manner. AS605240 suppresses in a dose-dependent manner the proliferation of BDC2.5 CD4+ T cells.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

AS605240 | AS 605240

Quick Database Links

Gene Symbol

PI3K