- 生物活性
Salinomycin sodium salt (Salinomycin sodium)，一种钾离子载体抗生素，是 Wnt/β-catenin 信号传导的有效抑制剂。Salinomycin sodium salt (Salinomycin sodium) 作用于 Wnt/Fzd/LRP 复合物，阻断 Wnt 诱导的 LRP6 磷酸化，导致 LRP6 蛋白降解。Salinomycin sodium salt (Salinomycin sodium) 选择性抑制人肿瘤干细胞。
- 靶点
Wnt/β-catenin
- 体外研究
Salinomycin (0.1-8 µM) inhibits the growth of HUVECs in a dose-dependent manner, accounting for 32.1 and 59.2% inhibition at 4 and 8 µM, respectively. HUVECs exposed to 2, 4 and 8 µM of Salinomycin for 48 h show a dose-dependent reduction in cell number and a change in cell morphology. Salinomycin (4 µM) treatment effectively inhibits HUVEC migration and invasion, and significantly disrupt the capillary-like tube formation of HUVECs. Salinomycin significantly suppresses the expression levels of phosphorylated (p)-FAK in a time- and dose-dependent manner in HUVECs. Salinomycin inhibits HUVEC angiogenesis by disturbing the VEGF-VEGFR2-AKT signaling axis. Combination of RSVL and Salinomycin synergistically inhibits the proliferation of TNBC (MDA-MB-231) cells. RSVL and Salinomycin effectively reduce wound healing, colony and tumorosphere forming capability in TNBC cells. Synergistic combination of RSVL and Salinomycin induces apoptosis in both culture conditions by significant upregulation of Bax with decreased Bcl-2 expression as comparison to untreated and alone drug treatments. Salinomycin (0, 2, 4, 8 and 16 μM) significantly inhibits the proliferation of A2780 and SK-OV-3 cell lines in a dose- and time-dependent manner, (IC
50 24h
: 13.8 μM, IC
50 48h
: 6.888 μM and IC
50 72h
: 4.382 μM for A2780 cell lines), (IC
50 24h
: 12.7 μM, IC
50 48h
: 9.869 μM and IC
50 72h
: 5.022 μM for SK-OV-3 cell lines). Salinomycin blocks the Wnt/β-catenin pathway in EOC cells. Salinomycin (2 μM) reduces cancer cell proliferation, inhibits STAT3 phosphorylation and P38 and β-catenin expressions, and suppresses epithelial-mesenchymal transition in colorectal cancer cells. Salinomycin (1-5 μM) inhibits cancer cell proliferation and STAT3 signaling in colorectal cancer cells. Furthermore, Salinomycin activates Akt (Ser 473) and down-regulates Hsp27 (Ser 82) phosphorylation in HT-29 and SW480. Salinomycin down-regulates hTERT and reduces telomerase activity when combined with telomerase inhibitor.
- 体内研究
Salinomycin (5 and 10 mg/kg) significantly supresses the average tumor volume and tumor weight. Salinomycin hinders the U251 human glioma cell growth in vivo via inhibition of angiogenesis with involvement of AKT and FAK dephosphorylation. Salinomycin (0.5 mg/kg b.wt.) enhances the mean survival time of the tumor bearing Swiss albino mice.
- 化学性质
白色或淡黄色结晶性粉末，微有特异臭，熔点140-142℃。易溶于丙酮、三氯甲烷、苯、乙酸乙酯、乙醚和甲醇，几乎不溶于水。大白鼠经口LD
50
70-100mg/kg，小白鼠经口LD
50
50mg/kg，鸡LD
50
150mg/kg。
- 盐霉素钠是安全有效的抗球虫药，对大多数革兰阳性菌也有抑制作用，对鸡的球虫、柔嫩艾氏、毒害艾氏、巨型艾氏、堆形艾氏和哈氏球虫均有效。可用于鸡饲料，用量为50-60g/t，产蛋期禁用，停药期5天。马属动物忌用，用后会致死；禁止与泰妙菌素、竹桃霉素同时使用。
Salirasib是一种有效的竞争性prenylated protein methyltransferase (PPMTase)抑制剂，Ki为2.6 μM，其抑制Ras甲基化，具有抗肿瘤活性并可诱导凋亡，用于生命科学领域；体外研究显示其抑制人Ha-ras转化的Rat1细胞生长，抑制Rat-1成纤维细胞、Ras转化的Rat-1及B16黑色素瘤细胞中Ras甲基化，降低细胞膜中Ras水平，抑制Ras依赖性细胞生长，干扰Raf-1和MAPK活化并抑制DNA合成；体内研究显示其在Panc-1异种移植裸鼠中显著抑制肿瘤生长且无全身毒性，在雄性Wistar大鼠中显著抑制硫代乙酰胺诱导的肝硬化，在先天性肌营养不良的dy(2J)/dy(2J)小鼠模型中减弱纤维化并提高肌肉力量。
