| 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(xì)胞實(shí)驗(yàn) | In vitro testing is performed using DIMSCAN (Only for Reference) |
| 激酶實(shí)驗(yàn) | 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(xì)胞用 LCL161 (1000-160000 nM) 和 PKC412 (2.5-40 nM) 處理 3 天，通過 trypan blue exclusion 檢測細(xì)胞活力。
結(jié)果：當(dāng)單獨(dú)給藥時，LCL161 適度抑制細(xì)胞的生長。LCL161 和 PKC412 聯(lián)合治療 MOLM13-luc+ 細(xì)胞比單獨(dú)使用任何一種藥物都能顯著殺死更多的細(xì)胞，Calcusyn 聯(lián)合指數(shù)表明存在協(xié)同作用。[1]
方法：NSCLC 細(xì)胞 A549 和 H460 用 LCL161 (10 μM) 和 paclitaxel (10 μM) 處理 48 h，flow cytometry 檢測細(xì)胞凋亡。
結(jié)果：與單獨(dú)用 LCL161 或 paclitaxel 治療的細(xì)胞相比，LCL161/paclitaxel 聯(lián)合治療組的細(xì)胞凋亡顯著降低。[2] |
| 體內(nèi)活性 | 方法：為檢測體內(nèi)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(xì)胞的 NCr nude 小鼠，給藥七天。
結(jié)果：LCL161 顯著增強(qiáng)了 PKC412 在體內(nèi)抑制 Ba/F3-FLT3-ITD-luc+ 細(xì)胞生長的能力。PKC412 或 LCL161 單獨(dú)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(dú)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
Powder: -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(guān)鍵字 | LCL-161 | LCL161 | LCL 161 | Inhibitor | inhibit | IAP | cIAP |
| 相關(guān)產(chǎn)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(guān)庫 | 抑制劑庫 | 經(jīng)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(xì)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 |