AS-605240 is a specific and orally active inhibitor of thePI3Kγ, with anIC₅₀of 8 nM, and aK_iof 7.8 nM.

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 IC₅₀of 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^[2].

AS-605240 (30 mg/kg BW, per os, every 12 h) markedly decreases FoxM1 expression in mouse lungs and fails to restore vascular integrity^[1]. AS-605240 reduces RANTES-induced peritoneal neutrophil recruitment, with ED₅₀of 9.1 mg/kg. In the CCL5 model, AS-605240 shows an ED₅₀value 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^[2]. 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^[3]. 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^[4].

257.27

Solid

C₁₂H₇N₃O₂S

648450-29-7

Room temperature in continental US; may vary elsewhere.

DMSO : 25 mg/mL(97.17 mM;ultrasonic and adjust pH to 10 with NaOH)

H₂O : 2.78 mg/mL(10.81 mM;ultrasonic and warming and adjust pH to 10 with NaOH and heat to 60℃)

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 0.5%CMC-Na  0.5%Tween-80

  Solubility: 6.25 mg/mL (24.29 mM); Suspened solution; Need ultrasonic
• 2.

  请依序添加每种溶剂： 10% DMSO    40%PEG300   5%Tween-80   45% saline

  Solubility: 2.5 mg/mL (9.72 mM); Suspended solution; Need ultrasonic

  此方案可获得 2.5 mg/mL (9.72 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH2O 中，得到澄清透明的生理盐水溶液
• 3.

  请依序添加每种溶剂： 10% DMSO    90% (20%SBE-β-CDin saline)

  Solubility: ≥ 2.5 mg/mL (9.72 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (9.72 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明