| 名稱 | LCL161 |
| 描述 | LCL161 is a SMAC mimetic, an IAP antagonist with oral activity that inhibits XIAP (IC50=35 nM) in HEK293 cells and also inhibits cIAP1 (IC50=0.4 nM) in MDA-MB-231 cells. LCL161 has potential antitumor activity. |
| 細胞實驗 | In vitro testing is performed using DIMSCAN (Only for Reference) |
| 激酶實驗 | CYP3A activity is assessed using the probe reactions, midazolam-1′-hydroxylation and testosterone 6β-hydroxylation. For reversible inhibition, incubations (37°C, 10 min) are composed of (final concentrations): potassium phosphate buffer (100 mM, pH 7.4), β-NADPH (1 mM), magnesium chloride (5 mM), microsomal protein (0.025 mg/mL), probe substrate (1 μM midazolam or 25 μM testosterone), LCL161 (0, 0.5, 1, 5, 10, 25, 50, or 100 μM) and organic solvent (0.2% acetonitrile for midazolam, 0.2% methanol for testosterone). After a 3-minute preincubation, the reactions are initiated by addition of β-NADPH and terminated by addition of acetonitrile (two volumes). Reactions are previously shown to be linear with respect to time and protein concentration (results not shown) with midazolam and testosterone turnover of 8.7±1.3% (n=3) and 2.6±0.20%, respectively. Formation of 1′-hydroxymidazolam and 6β-hydroxytestosterone is determined by LC-MS/MS as described below[3]. |
| 體外活性 | 方法：MOLM13 細胞用 LCL161 (1000-160000 nM) 和 PKC412 (2.5-40 nM) 處理 3 天，通過 trypan blue exclusion 檢測細胞活力。
結果：當單獨給藥時，LCL161 適度抑制細胞的生長。LCL161 和 PKC412 聯(lián)合治療 MOLM13-luc+ 細胞比單獨使用任何一種藥物都能顯著殺死更多的細胞，Calcusyn 聯(lián)合指數表明存在協(xié)同作用。[1]
方法：NSCLC 細胞 A549 和 H460 用 LCL161 (10 μM) 和 paclitaxel (10 μM) 處理 48 h，flow cytometry 檢測細胞凋亡。
結果：與單獨用 LCL161 或 paclitaxel 治療的細胞相比，LCL161/paclitaxel 聯(lián)合治療組的細胞凋亡顯著降低。[2] |
| 體內活性 | 方法：為檢測體內抗腫瘤活性，將 LCL161 (50 mg/kg，每天兩次) 和 PKC412 (40 mg/kg，每天一次) 灌胃給藥給注射 Ba/F3-FLT3-ITD-luc+ 腫瘤細胞的 NCr nude 小鼠，給藥七天。
結果：LCL161 顯著增強了 PKC412 在體內抑制 Ba/F3-FLT3-ITD-luc+ 細胞生長的能力。PKC412 或 LCL161 單獨抑制白血病生長與 PKC412+LCL161 聯(lián)合抑制白血病生長之間的差異也很顯著。PKC412+LCL161 治療的小鼠的脾臟重量百分比小于單獨使用載體或任何一種藥物治療的小鼠。[1] |
| 存儲條件 | Keep away from direct sunlight,Store at low temperature,Store under nitrogen
Pure form: -20°C for 3 years | In solvent: -80°C for 1 year
Shipping with blue ice/Shipping at ambient temperature. |
| 溶解度 | DMSO : 93 mg/mL (185.77 mM), Sonication is recommended.
Ethanol : 16 mg/mL (31.96 mM), Sonication is recommended.
H2O : < 1 mg/mL (insoluble or slightly soluble)
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| 關鍵字 | LCL-161 | LCL161 | LCL 161 | Inhibitor | inhibit | IAP | cIAP |
| 相關產品 | 1-Monopalmitin | A 410099.1 | Acacetin | （Iso）-Flavokawain A | Xevinapant | 4-Methylsalicylic acid | UC-112 | Embelin | N-Deshydroxyethyl Dasatinib | Se-Methylselenocysteine | AZD5582 TFA | HM90822 |
| 相關庫 | 抑制劑庫 | 經典已知活性庫 | 抗癌活性化合物庫 | 抗癌化合物庫 | 已知活性化合物庫 | 臨床失敗化合物庫 | 含氟化合物庫 | 細胞凋亡化合物庫 | 抗衰老化合物庫 | 藥物功能重定位化合物庫 | 抗癌臨床化合物庫 | 抗癌藥物庫 |