| 名稱 | SN-38 |
| 描述 | SN-38 (NK012) is the active metabolite of Irinotecan, a DNA topoisomerase I (Topo I) inhibitor, which inhibits DNA and RNA synthesis (IC50=0.077/1.3 μM). SN-38 has antitumor activity and induces autophagy. |
| 細(xì)胞實(shí)驗(yàn) | MTT assay(Only for Reference) |
| 激酶實(shí)驗(yàn) | Topoisomerase I Assay: One unit (the minimum amount for full relaxation of 0.5 μg SV40 DNA under the conditions of this study) of topoisomerase I, 0.5 μL of the test compounds, and 0.5μg SV40 DNA are added sequentially to the reaction buffer, which is composed of 25 mM Tris-HCl (pH 7.5), 50 mM KC1, 5 mM MgCl2, 0.25 mM EDTA disodium salt, 0.25 mM dithiothreitol, 15μg /mL bovine serum albumin, and 5% glycerol. Then, the reaction mixture (50 μL) is incubated for 10 min at 37 °C, and the reaction is terminated by treatment with 7.5 μL of a solution consisting of 1% sodium dodecyl sulfate, 20 mM EDTA disodium salt, and 0.5 mg/mL proteinase K for an additional 30 min at 37°C. The samples are mixed with 5 μL of the loading buffer containing 10 mM Na2HPO4, 31.3% sucrose, and 0.3% bromophenol blue. Relaxed (form Ir) DNA is separated from supercoiled (form I) and nicked (form II) DNA by electrophoresis on 0.8% agarose gel at 50 mA and 20 V for 17 h in the presence of 2 μg/mL chloroquine, 10 mM EDTA, 30 mM NaH2PO4, and 36 Mm Tris-HCl (pH 7.8). After electrophoresis, the gel is stained with 0.05% ethidium bromide and photographed with UV light (302 nm). The amount of DNA is quantified using a densitometer. |
| 體外活性 | 方法：肺癌細(xì)胞 LLC、A549 和 H358 用 SN-38 (10-1000 nM) 處理 48 h，使用 MTT assay 檢測細(xì)胞活力。
結(jié)果：SN-38 在 10 nM 濃度下開始表現(xiàn)出作用，并在 100 nM 下誘導(dǎo)約 50% 的細(xì)胞死亡。[1]
方法：結(jié)直腸癌細(xì)胞 KM12C、KM12SM 和 KM12L4a 用 SN-38 (2.5 μg/mL) 處理 4-48 h，使用 Flow cytometry 檢測細(xì)胞周期和凋亡。
結(jié)果：SN-38 誘導(dǎo)的 S 期和 G2 期阻滯，KM12L4a 細(xì)胞以時(shí)間依賴性反應(yīng)最強(qiáng)。KM12SM 和 KM12L4a 細(xì)胞系的凋亡率隨時(shí)間增加，但在 KM12C 細(xì)胞中沒有這種變化。[2] |
| 體內(nèi)活性 | 方法：為檢測體內(nèi)抗腫瘤活性，將 SN-38 (2 mg/kg) 單次腹腔注射給腹膜腔內(nèi)移植 LLC 細(xì)胞的 C57BL/6 小鼠。
結(jié)果：單次腹腔注射 SN-38 可顯著減弱 LLC 腫瘤的生長，使腫瘤生長減少 22.7%。[1]
方法：為檢測體內(nèi)抗腫瘤活性，將 SN-38 (10 mg/kg in 0.5% carboxymethylcellulose sodium，腹腔注射) 和 gefitinib (100 mg/kg，皮下注射) 攜帶人口腔鱗狀腫瘤 HSC-2 的 BALB/c nude 小鼠，每周五次，持續(xù)三周。
結(jié)果：僅 gefitinib 治療和 gefitinib 加 SN-38 治療在腫瘤生長抑制方面沒有顯著差異。然而，當(dāng)治療停止后繼續(xù)進(jìn)行腫瘤測量時(shí)，僅吉非替尼組的一些腫瘤顯示出新的生長。[3] |
| 存儲(chǔ)條件 | Store at low temperature
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Shipping with blue ice/Shipping at ambient temperature. |
| 溶解度 | Ethanol : < 1 mg/mL (insoluble)
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 3.93 mg/mL (10.02 mM), Suspension.
DMSO : 50.00 mg/mL (127.42 mM), Sonication is recommended.
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| 關(guān)鍵字 | Topoisomerase | Topo I | SN-38 | SN38 | RNASynthesis | RNA Synthesis | NK-012 | NK 012 | Inhibitor | inhibit | DNASynthesis | DNA synthesis | Autophagy | ADCCytotoxin | ADC Payload | ADC Cytotoxin |
| 相關(guān)產(chǎn)品 | Hexane-1,6-diol | Guanidine hydrochloride | Naringin | Aceglutamide | Alginic acid | Hemin | Hydroxychloroquine | Sildenafil citrate | Stavudine | Tamoxifen | Thymidine | Paeonol |
| 相關(guān)庫 | 抑制劑庫 | 抗乳腺癌化合物庫 | 抗癌活性化合物庫 | 經(jīng)典已知活性庫 | 已知活性化合物庫 | 生物堿類天然產(chǎn)物庫 | 抗癌天然產(chǎn)物庫 | 抗衰老化合物庫 | 血液病分子庫 | 藥物功能重定位化合物庫 | 抗癌臨床化合物庫 | 抗癌藥物庫 |