| 名稱 | WP1066 |
| 描述 | WP1066 is a inhibitor of JAK2 (IC50: 2.30 μM) and STAT3 (IC50: 2.43 μM) in HEL cells; shows activity to JAK2, STAT3/5, and ERK1/2, not JAK1 and JAK3. WP1066 has been used in trials studying the treatment of Melanoma, Brain Cancer, Solid Tumors, and Central Nervous System Neoplasms. |
| 細(xì)胞實驗 | The 3, [4,5-dimethylthiazol-2-yl]-5-[3-carboxymethoxyphenyl]-2-[4-sulfophenyl]-2H-tetrazolium (MTT) assay is done using an MTT-based cell proliferation/cytotoxicity assay system. Briefly, fresh low-density peripheral blood cells and various cell lines at the logarithmic phase of their growth are washed twice in RPMI 1640 containing 10% FCS and counted in a hemocytometer. Cell viability is assessed by the trypan blue (0.1%) staining method. Equal numbers of viable cells (5 × 104 per well) are incubated in a total volume of 100 μL of RPMI 1640 supplemented with 10% FCS alone or with WP1066 at increasing concentrations; the incubations are continued for up to 72 h in 96-well flat-bottomed plates at 37 °C in a humidified 5% CO2 atmosphere. Experiments for each condition are done in triplicate. After incubation, 20 μL of CellTiter96 One Solution Reagent are added to each well. The plates are then incubated for an additional 60 min at 37 °C in a humidified 5% CO2 atmosphere. Immediately after incubation, absorbance is read using a 96-well plate reader at a wavelength of 490 nm.(Only for Reference) |
| 體外活性 | WP1066能劑量依賴性地顯著抑制攜帶JAK2 V617F突變亞型的HEL細(xì)胞的生長（IC20/IC50/IC80：0.8/2.3/3.8 μM）。在表達JAK2 V617F突變亞型的急性白血病HEL細(xì)胞中,WP1066（0.5-4.0 μM）可抑制JAK2, STAT3, STAT5及ERK1/2的磷酸化,但對JAK1和JAK3的磷酸化無抑制作用。WP1066（0.5-3.0 μM）,以劑量依賴性地抑制從病人體內(nèi)獲得的AML形細(xì)胞以及AML細(xì)胞系OCIM2和K562的增殖。濃度在0.5, 1.0, 2.0, 3.0或4.0 μM時的WP1066在OCIM2和K562細(xì)胞中,劑量依賴地降低JAK2和pJAK2的蛋白水平,同時STAT3,STAT5和AKT的磷酸化水平。WP1066（1,2或3 μM）可激活procaspase-3,裂開的PARP,劑量依賴地引起OCIM2和K562細(xì)胞的細(xì)胞凋亡。通過誘導(dǎo)處在細(xì)胞周期G0-G1期細(xì)胞的積累,WP1066（2 μM）可抑制OCIM2細(xì)胞增加。WP1066（5 μM）可阻止STAT3磷酸化,2.5 μM時能使Caki-1和 786-O腎癌細(xì)胞的生存和增殖受到顯著抑制。 WP1066（5 μM）還能抑制Caki-1和786-O腎癌細(xì)胞中HIF1α和HIF2α的表達及VEGF的產(chǎn)生。 |
| 體內(nèi)活性 | 在Caki-1移植小鼠中,連續(xù)服用19天WP1066（40 mg/kg/day,p.o.）可顯著抑制的腫瘤生長,同時減少磷酸化的STAT3免疫染色,并降低CD34陽性血管長度. |
| 存儲條件 | store at low temperature,keep away from direct sunlight | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | DMSO : 40 mg/mL (112.29 mM)
Ethanol : < 1 mg/mL (insoluble or slightly soluble)
|
| 關(guān)鍵字 | WP 1066 | STAT | inhibit | Inhibitor | JAK | Janus kinase | WP-1066 | Apoptosis | WP1066 |
| 相關(guān)產(chǎn)品 | Lidocaine hydrochloride | Metronidazole | 5-Fluorouracil | Stavudine | Tributyrin | Dextran sulfate sodium salt (MW 4500-5500) | Myricetin | Sorafenib | L-Ascorbic acid | Acetylcysteine | Sodium 4-phenylbutyrate | Kaempferol |
| 相關(guān)庫 | 抑制劑庫 | 抗癌活性化合物庫 | 經(jīng)典已知活性庫 | 已知活性化合物庫 | 激酶抑制劑庫 | 抗衰老化合物庫 | 藥物功能重定位化合物庫 | 酪氨酸激酶分子庫 | 抗癌臨床化合物庫 | 抗癌藥物庫 |