| 名稱 | AS-605240 |
| 描述 | AS-605240 is an effective and specific inhibitor of PI3Kγ (IC50/Ki: 87.8 nM). |
| 細(xì)胞實(shí)驗(yàn) | After a 3-hour starvation in serum-free medium, Cells are pretreated with AS-605240 or DMSO for 30 min and stimulated for 5 min with 50 nM of C5a. PKB phosphorylation is monitored using phosphorylated Ser473 Akt-specific antibody and standard ELISA protocols. (Only for Reference) |
| 激酶實(shí)驗(yàn) | In vitro PI3K lipid kinase assay: (1) For PI3Kγ: human PI3Kγ (100 ng) is incubated at RT with kinase buffer (10 mM MgCl2, 1 mM β-glycerophosphate, 1 mM DTT, 0.1 mM Na3VO4, 0.1% Na Cholate and 15 μM ATP/100 nCi γ[33P]ATP, final concentrations) and lipid vesicles containing 18 μM PtdIns and 250 μM of PtdSer (final concentrations), in the presence of AS-605240 or DMSO. Kinase reaction is stopped by adding 250 μg of Neomycin-coated Scintillation Proximity Assay (SPA) beads. (2) For PI3Kα, β, and δ: varying amounts of ATP are incubated with the different purified PI3K isoforms and saturating concentrations of PtdIns. Consequently, IC50 determinations with PI3Kα, β, and δ, to evaluate inhibitor selectivity are performed as follows: 60 ng of PI3Kα are incubated at RT with kinase buffer, as described for PI3Kγ (but containing 89 μM ATP/300 nCi γ[33P]ATP and no Na Cholate, instead) and lipid vesicles containing 212 μM PtdIns and 58 μM of PtdSer. 100 ng of PI3Kβ are incubated at RT with kinase buffer (containing 70 μM ATP/300 nCi γ[33P]ATP, 4 mM MgCl2 and no Na Cholate) and lipid vesicles containing 225 μM PtdIns and 45 μM of PtdSer. 90 ng of PI3Kδ are incubated with kinase buffer (containing 65 μM ATP/300 nCi γ[33P]ATP, 1 mM MgCl2, and no Na Cholate) and lipid vesicles containing 100 μM PtdIns and 170 μM of PtdSer. The reactions are stopped after 2 hours. |
| 體外活性 | 在肥胖癥誘導(dǎo)的糖尿病ob/ob鼠模型中,AS-605240（10 mg/kg）會(huì)降低血糖水平, 使胰島素敏感性和葡萄糖耐量顯著提高,且對(duì)體重?zé)o影響,30 mg/kg劑量的效果更好,對(duì)體重只有輕微影響.AS-605240使ATMs量和MCP-1循環(huán)水平降低. 在αCII誘導(dǎo)的關(guān)節(jié)炎中,AS-605240（50 mg/kg）保護(hù)其免受 αCII-IA癥狀.在膠原誘導(dǎo)的關(guān)節(jié)炎鼠模型中,AS-605240（50 mg/kg）也抑制關(guān)節(jié)炎癥和損傷.AS-605240可使RANTES誘導(dǎo)的患腹膜炎鼠體內(nèi)的中性粒細(xì)胞趨化性降低（ED50：9.1 mg/kg）. |
| 體內(nèi)活性 | 在骨髓單核細(xì)胞中,AS-605240（1 μM）對(duì)MCP-1或CSF-1誘導(dǎo)的PKB磷酸化有抑制作用。在鼠的SC-CA1突觸中,AS-605240（100 nM）消除NMDAR LTD,但對(duì)mGluR LTD和LTP無影響。AS-605240對(duì)PI3Kα/β/δ（IC50：60/270/300 nM）也有抑制作用。AS-605240還抑制C5a調(diào)節(jié)的PKB磷酸化（IC50：90 nM）。 |
| 存儲(chǔ)條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | DMSO : 1 mg/mL, Sonication is recommended.
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| 關(guān)鍵字 | PI3K | inhibit | Inhibitor | Phosphoinositide 3-kinase | AS-605240 | AS605240 | Autophagy |
| 相關(guān)產(chǎn)品 | Oxyresveratrol | Guanidine hydrochloride | Naringin | Taurine | Gefitinib | Hydroxychloroquine | Curcumin | Stavudine | Paeonol | Sodium 4-phenylbutyrate |
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