| 名稱 | PIK-93 |
| 描述 | PIK-93 is the first potent, synthetic PI4K inhibitor with IC50 of 19 nM; inhibits PI3Kα with IC50 of 39 nM. |
| 細(xì)胞實驗 | For actin staining, dHL60 cells are preincubated in suspension with PIK-93 or vehicle for 40 min, centrifuged for 5 min at 2000 rpm at room temperature in a J6-B centrifuge, resuspended in mHBSS containing the respective agent at the same concentration, allowed to stick to fibronectin-covered coverslips, and subjected to stimulation with a uniform concentration of 100 nM f-Met-Leu-Phe (fMLP) for 3 min. Cellsare fixed in 3.7% PFA and stained with 10 units/mL rhodamine-phalloidin for 15 min.(Only for Reference) |
| 激酶實驗 | Assay of PI3Ks: IC50 values are measured using a standard TLC assay for lipid kinase activity. Kinase reactions are performed by preparing areaction mixture containing kinase, PIK-93 (2% DMSO final concentration), buffer (25 mM HEPES, pH 7.4, 10 mM MgCl2), and freshly sonicated phosphatidylinositol (100 μg/ml). Reactions are initiated by the addition of ATP containing 10 μCi of γ-32P-ATP to a final concentration 10 or 100 μM, and allowed to proceed for 20 min at room temperature. For TLC analysis, reactions are then terminated by the addition of 105 μL 1N HCl followed by 160 μL CHCl3:MeOH (1:1). The biphasic mixture is vortexed, briefly centrifuged, and the organic phase transferred to a new tube using a gel loading pipette tip precoated with CHCl3. This extract is spotted on TLC plates and developed for 3 hours–4 hours in a 65:35 solution of n-propanol:1M acetic acid. The TLC plates are then dried, exposed to a phosphorimager screen, and quantitated. Kinase activity is typically measured at 10–12 concentrations of PIK-93 representing two-fold dilutions from the highest concentration of 100 μM. |
| 體內(nèi)活性 | 0.5 μM-1 μM PIK-93作用于分化的HL60細(xì)胞,損害用f-Met-Leu-Phe處理而形成的聚集的穩(wěn)定性。在COS-7細(xì)胞中,PIK-93（250 nM）有效地消除了高爾基體中CERT-PH結(jié)構(gòu)域和FL-Cer的積累。在T6.11細(xì)胞中,300 nM PIK-93降低Carbachol誘導(dǎo)的TRPC6移位到質(zhì)膜上和Ca2+進(jìn)入。相同濃度PIK-93也明顯抑制[3H]絲氨酸標(biāo)記的內(nèi)源性神經(jīng)酰胺轉(zhuǎn)變?yōu)樯窠?jīng)鞘磷脂。這些說明了PI4KIIIβ在內(nèi)質(zhì)網(wǎng)和高爾基體中的神經(jīng)酰胺轉(zhuǎn)移時具有重要作用,以及有效調(diào)節(jié)鞘磷脂的合成。一項研究顯示,PIK-93具有抗腸道病毒功能,抑制脊髓灰質(zhì)炎病毒和丙型肝炎病毒復(fù)制,EC50分別為0.14 μM和1.9 μM。PIK-93有效抑制PI3Kγ和PI4KIIIβ,IC50分別為16 nM和19 nM。PIK-93也抑制其他PI3Ks成員,包括PI3Kα,β和δ,IC50分別為39 nM,0.59 μM和0.12 μM。而PIK-93對其他激酶幾乎沒有抑制效果,即使?jié)舛葹?0 μM。 |
| 存儲條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | DMSO : 39 mg/mL (100.03 mM), Sonication is recommended.
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| 關(guān)鍵字 | VirusProtease | Virus Protease | PIK-93 | PIK93 | PI4K | PI4 kinases | PI3KIIIβ | PI3K | Phosphoinositide 3-kinase | Phosphatidylinositol 4 kinases | p110δ | p110γ | p110β | p110α | mTORC1 | Inhibitor | inhibit | hsVps34 | DNA-PK | DNAPK | CarbonicAnhydrase | Carbonic Anhydrase | C2β | ATR | ATM |
| 相關(guān)產(chǎn)品 | Oxyresveratrol | Cyclamic acid sodium | 4-Phenylbutyric acid | Benzenesulfonamide | Anthraquinone | Levamisole hydrochloride | Myricetin | 2-Phenylethanol | L-Lysine | Cytarabine | Phenytoin sodium | Hydrochlorothiazide |
| 相關(guān)庫 | 抑制劑庫 | 經(jīng)典已知活性庫 | 已知活性化合物庫 | 抗癌細(xì)胞代謝庫 | 自噬庫 | 激酶抑制劑庫 | 抗衰老化合物庫 | 癌細(xì)胞分化化合物庫 | NO PAINS 化合物庫 | 抗病毒庫 | 免疫/炎癥分子化合物庫 | 抗前列腺癌化合物庫 |