| 名稱 | Fimepinostat |
| 描述 | Fimepinostat (CUDC 907) is an orally bioavailable inhibitor of both phosphoinositide 3-kinase (PI3K) class I and pan-histone deacetylase (HDAC) enzymes, with potential antineoplastic activity. Upon oral administration, CUDC-907 inhibits the activity of both PI3K class I isoforms and HDAC, thereby preventing the activation of the PI3K-AKT-mTOR signal transduction pathway that is often overactivated in many cancer cell types. |
| 細(xì)胞實(shí)驗(yàn) | CUDC-907 is dissolved in DMSO and stored (-80°C), and then diluted with appropriate medium before use[1]. Human cancer cell lines are plated at densities of 5,000 to 10,000 per well in 96-well flat-bottomed plates with the recommended culture medium. The cells are then incubated with compounds (e.g.,CUDC-907) at various concentrations for 72 hours in culture medium supplemented with 0.5% (v/v) FBS. Growth inhibition is assessed by assay of cellular ATP content using the Perkin-Elmer ATPlite kit[1]. |
| 激酶實(shí)驗(yàn) | The activities of classes I and II HDACs are measured using the Color-de-Lys assay system. The activity of PI3K is measured using the ADP-Glo luminescent kinase assay. Recombinant PI3K protein, a complex of N-terminal GST-tagged recombinant full-length human p110 and untagged recombinant full-length human p85, is coexpressed in a baculovirus-infected Sf9 cell expression system[1]. |
| 體外活性 | 在作用于NHL和MM模型的高效性研究中, CUDC-907按最大耐受劑量處理,比單獨(dú)藥劑PI3K或HDAC抑制劑或兩者聯(lián)用效果更明顯.且按最大耐受劑量處理,CUDC-907比PI3Kδ選擇性抑制劑CAL-101更有效.CUDC-907對犬類具有口服生物有效性.CUDC-907在小鼠腫瘤中的半衰期較長.作用于移植瘤時(shí),CUDC-907誘導(dǎo)凋亡并抑制癌細(xì)胞增殖. |
| 體內(nèi)活性 | CUDC-907對一系列B細(xì)胞淋巴瘤的生長具有抑制作用,如Granta 519（IC50：7 nM）,DOHH2（IC50：1 nM）,RL（IC50：2 nM）,Pfeiffer（IC50：4 nM）,SuDHL4（IC50：3 nM）,Daudi（IC50：15 nM） 和 Raji（IC50：9 nM）。CUDC-907對骨髓瘤增殖也有阻斷作用,如RPMI8226（IC50：2 nM）,OPM-2（IC50：1 nM）和ARH77（IC50：5 nM）。CUDC-907對多發(fā)性骨髓瘤和B細(xì)胞淋巴瘤均有明顯抗癌活性。CUDC-907對其他PI3K亞型有抑制作用抑制,如 PI3Kβ/γ/δ和 PI3KαE545K, IC50分別為 54/311/39/62 nM。而且, CUDC-907對HDAC亞型HDAC8//6/11（IC50：191/27/5.4 nM）也有抑制效果。此外,CUDC-907對其他類型 HDAC 酶活性也有微弱抑制。 |
| 存儲條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Shipping with blue ice/Shipping at ambient temperature. |
| 溶解度 | 10% DMSO+90% (20% SBE-β-CD in Saline) : < 6.25 mg/mL (12.29 mM), Lower concentrations may be soluble, but exact solubility limit is unknown.
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 10 mg/mL (19.66 mM), Suspension.
Ethanol : < 1 mg/mL (insoluble or slightly soluble)
10% DMSO+90% Saline : < 6.25 mg/mL (12.29 mM), Lower concentrations may be soluble, but exact solubility limit is unknown.
10% DMSO+90% Corn oil : 6.25 mg/mL (12.29 mM), Solution.
DMSO : 62.5 mg/mL (122.9 mM), Sonication is recommended.
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| 關(guān)鍵字 | PI3K | Phosphoinositide 3-kinase | Inhibitor | inhibit | Histone deacetylases | HDAC3 | HDAC2 | HDAC11 | HDAC10 | HDAC1 | HDAC | Fimepinostat | CUDC907 | Apoptosis |
| 相關(guān)產(chǎn)品 | Formamide | Urea | Dimethyl phthalate | Aceglutamide | Alginic acid | Cysteamine hydrochloride | Manganese chloride (tetrahydrate) | Metronidazole | Sildenafil citrate | Citric Acid Triammonium | Stavudine | Tamoxifen |
| 相關(guān)庫 | 抑制劑庫 | 經(jīng)典已知活性庫 | 抗癌活性化合物庫 | 已知活性化合物庫 | 激酶抑制劑庫 | 臨床失敗化合物庫 | 抗衰老化合物庫 | 免疫/炎癥分子化合物庫 | 藥物功能重定位化合物庫 | 抗癌臨床化合物庫 | 抗癌藥物庫 | 細(xì)胞重編程化合物庫 |