盐霉素 | 53003-10-4

• 物质功能分类: 原料药 - 抗寄生虫病药 - 抗原虫药
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 中文名称: 盐霉素
• 中文别名: 盐霉；沙利霉素；优素精；3-三氟甲基肉桂酰氯
• 英文名称: salinomycin
• 英文别名: SAL；salinomycinic acid；ovicox；K-748364A；K-364；AHR-3096；coxistac；salocin；(2R)-2-[(2R,5S,6R)-6-[(2S,3S,4S,6R)-6-[(3S,5S,7R,9S,10S,12R,15R)-3-[(2R,5R,6S)-5-ethyl-5-hydroxy-6-methyloxan-2-yl]-15-hydroxy-3,10,12-trimethyl-4,6,8-trioxadispiro[4.1.57.35]pentadec-13-en-9-yl]-3-hydroxy-4-methyl-5-oxooctan-2-yl]-5-methyloxan-2-yl]butanoic acid
• CAS: 53003-10-4
• 化学式: C₄₂H₇₀O₁₁
• 分子量: 751.011
• InChiKey: KQXDHUJYNAXLNZ-XQSDOZFQSA-N

物化性质

• 熔点：
  112.5-113.5 °C(lit.)
• 比旋光度：
  D25 -63° (c = 1 in ethanol)
• 沸点：
  839.2±65.0 °C(Predicted)
• 密度：
  1.18±0.1 g/cm3(Predicted)
• 闪点：
  >110°(230°F)
• 溶解度：
  不溶于水；乙醇中≥142.2 mg/mL； DMSO 中≥91.8 mg/mL
• LogP：
  5.596 (est)
• 蒸汽压力：
  6.37X10-23 mm Hg at 25 °C (est)
• 稳定性/保质期：
  Stable under recommended storage conditions.
• 旋光度：
  Specific optical rotation = -63 deg at 25 °C/D (sodium) line (c = 1 in ethanol)
• 分解：
  When heated to decomposition it emits acrid smoke and irritating fumes.
• 解离常数：
  pKa = 4.5 (est)
• 碰撞截面：
  268.38 Ų [M-H]-; 266.44 Ų [M+Na]+

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  53
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  161
• 氢给体数：
  4
• 氢受体数：
  11

ADMET

代谢

... 硫酸盐霉素（SAL），一种广谱抗生素和球虫抑制剂，被发现比现有的化疗药物（如紫杉醇和阿霉素）能更有效地对抗肿瘤耐药性和杀死癌症干细胞；这重新聚焦了它对人类癌症治疗的重要性。在这项研究中，我们研究了SAL的体外药物代谢和药代动力学参数。SAL在肝脏微粒体中迅速代谢，具有高内源性清除率。SAL的代谢主要由CYP酶介导；CYP3A4是主要的代谢SAL的酶。与小鼠和大鼠血浆相比，SAL在人血浆中的血浆蛋白结合率显著较低。通过化学抑制和重组酶研究进行了CYP抑制。发现SAL是CYP2D6以及CYP3A4的中等抑制剂。由于CYP3A4是主要负责SAL代谢的酶，因此在大鼠中进行了体内药代动力学研究，以检查酮康唑（KTC）的伴随给药对SAL药代动力学的影响。KTC作为一种选择性的CYP3A4抑制剂，在伴随KTC给药的大鼠中，显著增加了SAL的系统暴露，AUC0-a增加了7倍，SAL的Cmax增加了3倍。

... Salinomycin (SAL), a broad spectrum antibiotic and a coccidiostat has been found to counter tumour resistance and kill cancer stem cells with better efficacy than the existing chemotherapeutic agents; paclitaxel and doxorubicin. This refocused its importance for treatment of human cancers. In this study, we studied the in vitro drug metabolism and pharmacokinetic parameters of SAL. SAL undergoes rapid metabolism in liver microsomes and has a high intrinsic clearance. SAL metabolism is mainly mediated by CYP enzymes; CYP3A4 the major enzyme metabolising SAL. The percent plasma protein binding of SAL in human was significantly lower as compared to mouse and rat plasma. CYP inhibition was carried out by chemical inhibition and recombinant enzyme studies. SAL was found to be a moderate inhibitor of CYP2D6 as well as CYP3A4. As CYP3A4 was the major enzyme responsible for metabolism of SAL, in vivo pharmacokinetic study in rats was done to check the effect of concomitant administration of Ketoconazole (KTC) on SAL pharmacokinetics. KTC, being a selective CYP3A4 inhibitor increased the systemic exposure of SAL significantly to 7-fold in AUC0-a and 3-fold increase in Cmax of SAL in rats with concomitant KTC administration.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

识别和使用：盐霉素是一种兽药，用于预防肉鸡、烤鸡和后备鸡由艾美耳球虫属的Eimeria tenella、E. necatrix、E. acervulina、E. maxima、E. brunetti和E. mivati引起的球虫病。它也用于预防由Eimeria dispersa和E. lettyae引起的鹌鹑球虫病。人类接触和毒性：研究了盐霉素对人类非恶性细胞的细胞毒性和遗传毒性。使用来自10个人的原代人鼻粘膜细胞（单层和小型器官培养）和外围血淋巴细胞来研究盐霉素（0.1-175 uM）的细胞毒性，通过annexin-propidiumiodide-和MTT测试。彗星试验用于评估DNA损伤。此外，通过ELISA分析了白细胞介素-8的分泌。流式细胞仪和MTT检测显示，在10-20 uM的低盐霉素浓度下，鼻粘膜细胞和淋巴细胞具有显著的细胞毒性。没有观察到遗传毒性。IL-8分泌在5 uM时升高。在抗肿瘤治疗的浓度下观察到了盐霉素诱导的细胞毒性和促炎效应。动物研究：有多份报告称，当盐霉素意外喂给各种动物时，会导致致命的后果。在一个饲养600只48周龄种火鸡的五个房屋中，其中一个房屋突然爆发死亡率，怀疑与饲料有关。火鸡喘息并变得卧倒；受影响的火鸡中有21.7%死亡。组织学病变仅限于骨骼肌，包括变性和坏死，被认为是离子载体中毒的典型表现。从受影响的房屋中取出的饲料样本分析显示，每吨饲料中含有13.4至18.4克的盐霉素。为了进一步研究盐霉素对火鸡的影响，进行了五项为期7天的试验，分别使用336、24、24、40和40只7、11、15、27和32周龄的雄性火鸡。随着火鸡年龄的增长，盐霉素的毒性增强。当7周龄的火鸡被喂食含有44或66 ppm盐霉素的饲料时，84只中只有1只死亡；当27或32周龄的火鸡被喂食这些量时，20只中有13只死亡。在幼年时，22 ppm的盐霉素倾向于抑制生长速度，在老年时防止或减少生长并增加死亡率。也有报道称六匹马意外中毒。症状的范围，包括厌食、腹痛、虚弱和共济失调，与那些被相关离子载体蒙宁霉素中毒的马相似。在另一次中毒事件中，马被喂食了制造商错误准备的含有61 mg/kg盐霉素的浓缩物。所有马都出现了严重的临床中毒症状。尽管进行了治疗，但八匹马在三到六天内死亡。另外十匹马倒下并不得不被安乐死。只有六匹马幸存。实验室结果的主要特点是酶水平极高和碱中毒。最典型的临床变化是后肢瘫痪。还报告了一起猫因摄入含有盐霉素的干猫粮而引发的毒性多发性神经病的爆发。从823只猫或约1%的猫中收集了流行病学和临床数据。在21只受影响的猫进行了尸检。受影响的猫突然出现跛行和后肢瘫痪，然后是前肢。临床和病理检查表明是一种涉及感觉和运动神经的远端多发性神经病。在一群因长期摄入有毒水平的盐霉素而导致的中毒牛中，也报告了临床体征和病理变化。380头牛中有39头出现了与心力衰竭一致的体征，其中8头死亡。临床体征包括呼吸困难、呼吸急促、心动过速和运动不耐受。对两头牛进行了尸检，其中一头有提示充血性心力衰竭的宏观病变，即肺水肿、胸水和肝肿大。组织病理学显示，主要表现为广泛的心肌纤维萎缩和局灶性肥大以及间质和替代性纤维化的慢性心肌病。肝脏和肺部的病变与充血性心力衰竭一致。最后，报告了一群羊在食用含有盐霉素的饲料后100%死亡。在喂食的第二天早上，发现78只羊死亡，其中一只出现了惊厥。尸检显示肺充血和水肿，皱胃出血，肾脏苍白，心肌中有白色条纹。

IDENTIFICATION AND USE: Salinomycin is a veterinary drug used for the prevention of coccidiosis in broiler, roaster and replacement chickens caused by Eimeria tenella, E. necatrix, E. acervulina, E. maxima, E. brunetti and E. mivati. It is also used for the prevention of coccidiosis in quail caused by Eimeria dispersa and E. lettyae. HUMAN EXPOSURE AND TOXICITY: The cytotoxic and genotoxic effects of salinomycin were investigated in human non-malignant cells. Primary human nasal mucosa cells (monolayer and mini organ cultures) and peripheral blood lymphocytes from 10 individuals were used to study the cytotoxic effects of salinomycin (0.1-175 uM) by annexin-propidiumiodide- and MTT-test. The comet assay was performed to evaluate DNA damage. Additionally, the secretion of interleukin-8 was analyzed by ELISA. Flow cytometry and MTT assay revealed significant cytotoxic effects in nasal mucosa cells and lymphocytes at low salinomycin concentrations of 10-20 uM. No genotoxic effects could be observed. IL-8 secretion was elevated at 5 uM. Salinomycin-induced cytotoxic and pro-inflammatory effects were seen at concentrations relevant for anti-cancer treatment. ANIMAL STUDIES: There are numerous reports of fatal outcomes when salinomycin is accidently fed to various animals. A sudden outbreak of mortality in one house of 600 48-week-old male breeder turkeys on a five-house turkey breeder farm was suspected to be feed-related. The turkeys gasped and became recumbent; 21.7% of affected turkeys died. Histological lesions, limited to skeletal muscle, consisted of degeneration and necrosis and were judged compatible with ionophore toxicosis. Feed samples from the affected house were analyzed and shown to contain 13.4 to 18.4 g of salinomycin per ton of feed. To further study the effects of salinomycin on turkeys, five 7-day trials using 336, 24, 24, 40, and 40 male turkeys when 7, 11, 15, 27, and 32 weeks of age, respectively. Salinomycin became more toxic as the age of the turkeys increased. When 7-week-old turkeys were fed diets containing 44 or 66 ppm salinomycin, only 1 of 84 died; when turkeys 27 or 32 weeks of age were fed those amounts, 13 of 20 died. Salinomycin at 22 ppm tended to depress rate of growth at young ages and to prevent or decrease growth and to increase mortality at older ages. Accidental poisonings were also reported in six horses fed salinomycin. The range of signs, including anorexia, colic, weakness and ataxia bore similarities to those described in horses poisoned with the related ionophore monensin. In another poisoning, horses were fed a concentrate containing 61 mg/kg salinomycin as faulty prepared by the manufacturer. All horses developed severe clinical signs of intoxication. Despite therapy eight horses died within three to six days. Ten others became recumbent and had to be euthanized. Only six horses survived. The dominating laboratory results were very high enzyme levels and alkalosis. The most characteristic clinical change appeared as paralysis of the hindlimbs. An outbreak of toxic polyneuropathy in cats that had ingested dry cat food contaminated with salinomycin has also been reported. Epidemiologic and clinical data were collected from 823 cats, or about 1% of the cats at risk. In 21 affected cats, postmortem examination was performed. The affected cats had acute onset of lameness and paralysis of the hindlimbs followed by the forelimbs. Clinical and pathologic examination indicated a distal polyneuropathy involving both the sensory and motor nerves. The clinical signs and pathology in an outbreak of toxicity in feedlot cattle attributed to the ingestion of toxic levels of salinomycin over an extended period of 11 weeks have also been reported. Thirty-nine out of 380 cattle developed signs consistent with cardiac failure and 8 of these died. Clinical signs included dyspnea, tachypnea, tachycardia, and exercise intolerance. Two cattle were necropsied and in one there were macroscopic lesions suggestive of congestive heart failure, namely pulmonary edema, hydrothorax and hepatomegaly. Histopathology revealed a chronic cardiomyopathy characterized principally by extensive myocardial fiber atrophy with multifocal hypertrophy and interstitial and replacement fibrosis. Hepatic and pulmonary lesions were consistent with those of congestive cardiac failure. Finally, 100% mortality was reported in a herd of sheep that were given feed containing salinomycin. The morning after the feeding, 78 sheep were found dead and one of them showed convulsive seizures. Postmortem examination revealed pulmonary congestion and edema, hemorrhages in abomasum, large pale kidney and white streak lines in myocardium.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

肝细胞癌（HCC）是少数几种在过去几年中观察到发病率持续增加的癌症之一。药物耐药性是HCC治疗中的一个主要问题。在当前研究中，我们使用盐霉素（Sal）和5-氟尿嘧啶（5-FU）联合疗法对HCC细胞系Huh7、LM3和SMMC-7721以及裸鼠皮下肿瘤模型进行研究，以探讨Sal是否能增加肝癌细胞对传统化疗药物如5-FU的敏感性。Sal和5-FU的联合使用在体内外对肝脏肿瘤产生了协同的抗肿瘤效果。Sal逆转了5-FU诱导的CD133(+) EPCAM(+)细胞增加、上皮-间质转化以及Wnt/β-连环蛋白信号通路的激活。Sal和5-FU的联合可能为我们提供了一种新的方法，用于逆转HCC患者的药物耐药性治疗。

Hepatocellular carcinoma (HCC) is one of the few cancers in which a continuous increase in incidence has been observed over several years. Drug resistance is a major problem in the treatment of HCC. In the present study, we used salinomycin (Sal) and 5-fluorouracil (5-FU) combination therapy on HCC cell lines Huh7, LM3 and SMMC-7721 and nude mice subcutaneously tumor model to study whether Sal could increase the sensitivity of hepatoma cells to the traditional chemotherapeutic agent such as 5-FU. The combination of Sal and 5-FU resulted in a synergistic antitumor effect against liver tumors both in vitro and in vivo. Sal reversed the 5-FU-induced increase in CD133(+) EPCAM(+) cells, epithelial-mesenchymal transition and activation of the Wnt/beta-catenin signaling pathway. The combination of Sal and 5-FU may provide us with a new approach to reverse drug resistant for the treatment of patients with HCC.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

化疗对软组织肉瘤的治疗效果并不令人满意，这是由于它们的化疗敏感性较低。即便是第一线的化疗药物多柔比星（doxorubicin），其响应率也只有18-29%。近期研究表明，抗生素盐霉素（salinomycin），一种钾离子载体，是一种强大的化合物，能够耗尽像腺癌中的癌症干细胞（CSC）这样的化疗耐药细胞。在这里，我们评估了盐霉素对肉瘤细胞系的影响，分析了盐霉素单独治疗以及与多柔比星联合治疗的效果。为了评估盐霉素对纤维肉瘤、横纹肌肉瘤和平滑肌肉瘤细胞系的影响，细胞分别接受了单一和联合治疗。通过细胞活性检测、细胞周期分析、caspase 3/7和9活性检测来监测相应治疗的效果。此外，我们还分析了NF-kappaB活性；p53、p21和PUMA的转录水平，以及p53表达和丝氨酸15磷酸化。盐霉素与多柔比星的联合使用增强了caspase的激活并增加了亚G1期的细胞比例。联合治疗导致了更高的NF-kappaB活性，以及p53、p21和PUMA的转录增加，而盐霉素单一治疗并没有引起任何显著变化。盐霉素增加了肉瘤细胞系对细胞毒性药物多柔比星的化疗敏感性——即使在亚致死浓度下也是如此。这些发现支持了一种策略，即在联合使用盐霉素的情况下减少多柔比星的浓度，以减少毒性副作用。

Chemotherapy for soft tissue sarcomas remains unsatisfactory due to their low chemosensitivity. Even the first line chemotherapeutic agent doxorubicin only yields a response rate of 18-29%. The antibiotic salinomycin, a potassium ionophore, has recently been shown to be a potent compound to deplete chemoresistant cells like cancer stem like cells (CSC) in adenocarcinomas. Here, we evaluated the effect of salinomycin on sarcoma cell lines, whereby salinomycin mono- and combination treatment with doxorubicin regimens were analyzed. To evaluate the effect of salinomycin on fibrosarcoma, rhabdomyosarcoma and liposarcoma cell lines, cells were drug exposed in single and combined treatments, respectively. The effects of the corresponding treatments were monitored by cell viability assays, cell cycle analysis, caspase 3/7 and 9 activity assays. Further we analyzed NF-kappaB activity; p53, p21 and PUMA transcription levels, together with p53 expression and serine 15 phosphorylation. The combination of salinomycin with doxorubicin enhanced caspase activation and increased the sub-G1 fraction. The combined treatment yielded higher NF-kappaB activity, and p53, p21 and PUMA transcription, whereas the salinomycin monotreatment did not cause any significant changes. Salinomycin increases the chemosensitivity of sarcoma cell lines - even at sub-lethal concentrations - to the cytostatic drug doxorubicin. These findings support a strategy to decrease the doxorubicin concentration in combination with salinomycin in order to reduce toxic side effects.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

一个因子设计（2x3）被用来评估黄曲霉毒素（0、2.5和5毫克每千克）与盐霉素（1、60克每吨（909千克））之间的相互作用。每个处理有四个重复，每个重复10只小鸡。...在所测量的任何参数上，黄曲霉毒素与盐霉素之间没有观察到显著的相互作用。

A factorial design (2 by 3) was used to evaluate the interaction between aflatoxin (0, 2.5, & 5 mg per kg) & salinomycin (1, 60 g per ton (909 kg)). There were four replicates of 10 chicks per treatment. ... No significant interaction was observed between aflatoxin & salinomycin on any of the parameters measured.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

这项研究旨在探讨盐霉素联合长春新碱对Jurkat细胞增殖和凋亡的影响及其可能机制。通过CKK-8实验检测Jurkat细胞的增殖，使用流式细胞术来评估细胞凋亡。通过Western blot测量BCL-2、caspase-3和caspase-8的水平。结果显示，无论是单独使用还是联合使用，盐霉素或长春新碱均以剂量依赖性方式抑制Jurkat细胞的增殖。盐霉素联合长春新碱对细胞增殖的抑制作用比单独使用任一化合物更为明显（P<0.05）。Western blot分析显示，盐霉素和长春新碱联合使用显著降低了BCL-2蛋白的表达，并显著增加了caspase 3和caspase 8蛋白的表达。此外，盐霉素和长春新碱联合使用协同促进了Jurkat细胞的凋亡（P<0.05）。盐霉素和长春新碱联合使用协同抑制T细胞急性淋巴细胞性白血病Jurkat细胞的增殖并促进其凋亡。

This study was aimed to investigate the effect of salinomycin combined with vincristine on the proliferation and apoptosis of Jurkat cells and its possible mechanisms. The proliferation of Jurkat cells was examined by CKK-8 assay. Flow cytometry was used to assess cellular apoptosis. Levels of BCL-2, caspase-3, and caspase- 8 were measured by Western blot. The salinomycin or vincristine, either alone or in combination, inhibited the proliferation of Jurkat cells in a dose-dependent manner. Salinomycin combined with vincristine produced more obvious inhibition of cell proliferation than either compound used alone (P<0.05). Western blot analysis showed that the combined use of Sal and VCR reduced the expression of BCL-2 protein, and increased expression of caspase 3 and caspase 8 protein, more significantly. Furthermore, combination of Sal and VCR synergistally promoted apoptosis of the Jurkat cells (P<0.05). The combination of salinomycin and vincristine synergistically inhibits proliferation and promotes apoptosis of T-cell acute lymphoblastic leukemia Jurkat cells.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

向鸡口服和静脉注射沙拉沙星，以确定其血药浓度、动力学行为、生物利用度和组织残留。药物通过单次剂量20 mg kg-1体重的嗉囊内和静脉给药。口服给药后半小时，沙拉沙星的血清浓度达到最高，吸收半衰期(t0.5(ab))为3.64小时，消除半衰期(t0.5(beta))为1.96小时。嗉囊给药后的系统生物利用度为73.02%，表明鸡通过此途径吸收沙拉沙星的程度很高。静脉注射后，沙拉沙星的动力学可以用一个两室开放模型来描述，t1/2(alpha)为0.48小时，稳态分布体积(Vd ss)为3.28升/公斤，总体清除率(Cl(beta))为27.39毫升/公斤/分钟。体外测定的沙拉沙星与血清蛋白结合倾向为19.78%。连续两周给予鸡沙拉沙星预混剂(60 ppm)后，血清和组织中的沙拉沙星浓度低于单次嗉囊内给予纯沙拉沙星(20 mg kg-1体重)的浓度。沙拉沙星残留物在肝脏中含量最高，其次是肾脏、肌肉、脂肪、心脏和皮肤。除肝脏外，48小时后在组织中未检测到沙拉沙星残留，且72小时后已完全消失。

Salinomycin was administered to chickens orally and intravenously to determine blood concentration, kinetic behavior, bioavailability and tissue residues. The drug was given by intracrop and intravenous routes in a single dose of 20 mg kg-1 body-weight. The highest serum concentrations of salinomycin were reached half an hour after oral dosage with an absorption half-life (t0.5(ab)) of 3.64 hours and elimination half-life (t0.5(beta)) of 1.96 hours. The systemic bioavailability percentage was 73.02 per cent after intracrop administration, indicating the high extent of salinomycin absorption from this route in chickens. Following intravenous injection the kinetics of salinomycin can be described by a two-compartment open model with a t1/2(alpha) of 0.48 hours, Vd ss (volume of distribution) of 3.28 litre kg-1 and Cl(beta) (total body clearance) of 27.39 ml kg-1 min-1. The serum protein-binding tendency of salinomycin as calculated in vitro was 19.78 per cent. Salinomycin concentrations in the serum and tissues of birds administered salinomycin premix (60 ppm) for two weeks were lower than those after administration of a single intracrop dose of pure salinomycin (20 mg kg-1 bodyweight). The highest concentration of salinomycin residues were present in the liver followed by the kidneys, muscles, fat, heart and skin. No salinomycin residues were detected in tissues after 48 hours except in the liver and these had disappeared completely by 72 hours.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险等级：
  6.1(a)
• 危险品标志：
  T
• 安全说明：
  S45
• 危险类别码：
  R25
• WGK Germany：
  3
• 危险品运输编号：
  UN 3462 6.1/PG 2
• RTECS号：
  VO8620000
• 海关编码：
  2309901000
• 包装等级：
  II
• 危险类别：
  6.1(a)

制备方法与用途

抗生素：盐霉素

概述

盐霉素又名优素精，是由白色链霉菌培养液中提取的一种聚醚类抗生素，属离子载体型抗生素，通常以盐霉素钠盐的形式存在。其钠盐为白色或淡黄色结晶性粉末，微有特异臭味，性质稳定，不溶于水，易溶于丙酮、苯和甲醇。

药理作用

盐霉素是一种高效、广谱、低耐药性和低残留的抗生素，也是广谱抗球虫药。它对革兰氏阳性菌、真菌、病原虫、球虫等具有显著的杀菌或抑菌作用。盐霉素对鸡堆型、布氏、巨型、变位、毒害、柔嫩等艾美尔球虫均有明显效果，其抗球虫活性大致与莫能菌素和常山酮相似。含本品60mg/kg的饲料防病性能和增重效率大致与莫能菌素100mg/kg相等；高浓度（80mg/kg）盐霉素的免疫抑制强度与莫能菌素相同，对猪有明显的生长促进效应，但因安全范围窄而受到限制。抗球虫活性峰期在第一代早期裂殖体阶段（即感染第1～2天），球虫对其产生耐药性的速率缓慢。高浓度（120ppm）盐霉素能抑制宿主产生免疫力，但停药后，免疫功能可迅速恢复。

应用

对猪的试验表明，不足4月龄仔猪喂30～60mg/kg药料，4～6月龄仔猪喂60～80mg/kg药料，效果较好。此外，盐霉素还被广泛应用于鸡球虫病和促进畜禽生长。

甲基盐霉素

概述

与盐霉素相似，甲基盐霉素也是一种离子载体型抗生素，主要用于肉鸡抗球虫治疗。马及马属动物对甲基盐霉素极敏感，应禁用；火鸡及其他鸟类亦较敏感而不宜使用。本品限用于肉鸡。

生物活性

概述

盐霉素（Salinomycin）曾被用作抗球虫药，并具有抗癌和抗肿瘤干细胞的效果。它能够通过干扰药物转运体ABC、Wnt/β-catenin及其他CSC信号通路，杀死癌症干细胞；此外，其对Gram阳性的细菌具有抗菌活性。

体外研究

Salinomycin是一种从Streptomyces albus中分离的聚醚类离子载体型抗生素。它能有效杀死不同起源的人类癌细胞系，并诱导大量凋亡。

体内研究

概述

Salinomycin能够有效地消除癌症干细胞，从而诱导预处理过的和具有药物抗性的癌症部分临床回归。在某些情况下，它还表现为阳性的离子型和变时型试剂，能加大心输出量、左心室收缩压等生理指标。

风险与安全性

在哺乳动物中如马、猫、猪和羊驼，Salinomycin被报导在偶然的口服或吸入摄入的情况下具有相当大的毒性作用。人类可接受的每日摄入量为5 μg/kg，超过500 μg/kg的每日摄入量会对狗产生神经毒性。静脉注射200-250 μg/kg的Salinomycin三周（隔天注射）会导致肿瘤转移的部分消退，并仅有非常小的急性、长期副作用。

用途

盐霉素和甲基盐霉素主要用于抗球虫剂，治疗鸡球虫病及促进畜禽生长。

反应信息

• 作为反应物：
  描述：

  盐霉素 在 N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 72.0h， 生成
  参考文献：
  名称：

  盐霉素的合成修饰：选择性O-酰化和生物学评估。

  摘要：

  沙利霉素被重新引起了人们的兴趣，它是通过选择性靶向癌症干细胞来预防癌症复发的药物。提出了通过其羟基的单独修饰来产生改良的盐霉素类似物的策略。对所得文库对乳腺癌细胞系的剂量反应作用的评估表明，C20羟基的酰化可用于将IC50值降低至沙利霉素的IC50值的五分之一。

  DOI：

  10.1039/c3cc45983g
• 作为产物：
  描述：

  盐霉素酸 在 molecular sieve 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以70%的产率得到盐霉素
  参考文献：
  名称：

  高度立体控制的聚醚抗生素沙利霉素的全合成。40-甲氧基苄基的关键作用；（mpm）羟基官能团保护基

  摘要：

  沙利霉素是通过D1-葡萄糖，D-甘露醇和L-乳酸乙酯经C1-C9，C10-C17和C18-C30片段的偶联而合成的。苄型保护基以及区域和立体选择性反应起着至关重要的作用。

  DOI：

  10.1016/s0040-4039(00)80703-0

文献信息

• SUBSTITUTED 2,4 DIAMINO-QUINOLINE AS NEW MEDICAMENT FOR FIBROSIS, AUTOPHAGY AND CATHEPSINS B (CTSB), L (CTSL) AND D (CTSD) RELATED DISEASES
  申请人：Genoscience Pharma SAS

  公开号：EP3620164A1

  公开（公告）日：2020-03-11

  The present invention relates to novel 2-primary amino-4-secondary amino-quinoline derivatives, their manufacture, pharmaceutical compositions comprising them and their use as medicaments. The active compounds of the present invention can be useful as a medicament in the treatment and/or the decreasing and/or the prevention of fibrosis and/or fibrosis related diseases, or for use as a medicament in the treatment and/or the decreasing and/or the prevention of the autophagy and/or autophagy related diseases and for the inhibition of the autophagy flux, or for use in the inhibition of cathepsins B (CTSB), L (CTSL) and/or D (CTSD) and/or cathepsins B (CTSB), L (CTSL) and/or D (CTSD) related diseases; with the proviso that said compounds are not to be used for the treatment of any forms of cancers.

  本发明涉及新型2-初级氨基-4-次级氨基喹啉衍生物，其制备方法，包含它们的药物组合物以及它们作为药物的用途。本发明的活性化合物可用作药物治疗和/或减少和/或预防纤维化和/或与纤维化相关疾病，或用作药物治疗和/或减少和/或预防自噬和/或与自噬相关疾病以及抑制自噬通量，或用于抑制蛋白酶B（CTSB）、L（CTSL）和/或D（CTSD）和/或与蛋白酶B（CTSB）、L（CTSL）和/或D（CTSD）相关疾病；但所述化合物不得用于治疗任何形式的癌症。
• 3-(BENZOIMIDAZOL-2-YL)-INDAZOLE INHIBITORS OF THE WNT SIGNALING PATHWAY AND THERAPEUTIC USES THEREOF
  申请人：Samumed, LLC

  公开号：US20140194441A1

  公开（公告）日：2014-07-10

  Indazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present disclosure concerns the use of an indazole compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, Alzheimer's disease, lung disease and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as genetic diseases and neurological conditions/disorders/diseases due to mutations or dysregulation of the Wnt pathway and/or of one or more of Wnt signaling components. Also provided are methods for treating Wnt-related disease states.

  揭示了用于治疗各种疾病和病理的吲唑化合物。更具体地，本公开涉及使用吲唑化合物或其类似物治疗由Wnt途径信号激活所特征的疾病（例如癌症、异常细胞增殖、血管生成、阿尔茨海默病、肺部疾病和骨关节炎），调节由Wnt途径信号介导的细胞事件，以及由于Wnt途径和/或一个或多个Wnt信号组分的突变或失调而导致的遗传疾病和神经系统疾病/疾患/疾病。还提供了治疗与Wnt相关疾病状态的方法。
• Synthesis and biological evaluation of 20-epi-amino-20-deoxysalinomycin derivatives
  作者：Yu Li、Qiuyan Shi、Jiajia Shao、Yaping Yuan、Zhigang Yang、Shizhen Chen、Xin Zhou、Shijun Wen、Zhong-Xing Jiang

  DOI：10.1016/j.ejmech.2018.02.004

  日期：2018.3

  To improve the druggability of salinomycin, a 20-epi-amino-20-deoxysalinomycin derivatives library was synthesized with high efficacy from which a few salinomycin derivatives with high potency and selectivity were identified through comprehensive cytotoxicity assay, including a fluorine-19 magnetic resonance sensitive tool molecule. Using a K-ras cellular model, salinomycin and its derivatives showed

  为了提高沙利霉素的可药性，合成了一个高效的20-表皮氨基20-脱氧沙利霉素衍生物库，通过全面的细胞毒性试验，包括对氟19磁共振敏感的方法，从中鉴定出了几种具有高效能和选择性的沙利霉素衍生物。工具分子。从文献报道来看，使用K-ras细胞模型，沙利霉素及其衍生物显示出不同的分子作用方式。这些结果对于开发基于盐霉素的癌症疗法将是有价值的。
• FUSED BICYCLIC HETEROCYCLE DERIVATIVES AS PESTICIDES
  申请人：Bayer Aktiengesellschaft

  公开号：US20200383334A1

  公开（公告）日：2020-12-10

  The invention relates to novel compounds of the formula (I) in which Aa, Ab, Ac, Ad, Q, R 1 and n have the definitions given above, to their use as acaricides and/or insecticides for controlling animal pests and to processes and intermediates for their preparation.

  这项发明涉及公式（I）的新化合物， 其中Aa、Ab、Ac、Ad、Q、R1和n具有上述给定的定义， 以及它们作为杀螨剂和/或杀虫剂用于控制动物害虫的用途，以及用于它们制备的工艺和中间体。
• [EN] INSECTICIDAL METHODS USING NITROGEN-CONTAINING HETEROAROMATIC COMPOUNDS<br/>[FR] PROCÉDÉS INSECTICIDES UTILISANT DES COMPOSÉS HÉTÉROAROMATIQUES CONTENANT DE L'AZOTE
  申请人：BASF SE

  公开号：WO2011064188A1

  公开（公告）日：2011-06-03

  Insectical methods using nitrogen containing heteroaromatic compounds The present invention relates to new insecticidal methods of using nitrogen-containing heteroaromatic compounds of the formula (I), wherein A, E, G, M, W, Y, X, R1 and R2 are defined as in the description, and to their enantiomers, diastereomers and agriculturally and veterinary acceptable salts. The present invention relates to methods of administering and applying such Pyridine compounds of formula I for insecticidal use and purposes in agriculture and in the veterinary field. The invention relates also to new derivatives of Pyridine compounds of formula I.

  使用含氮杂芳化合物的杀虫方法。本发明涉及使用式(I)的含氮杂芳化合物的新杀虫方法，其中A、E、G、M、W、Y、X、R1和R2如描述中所定义，并且其对映异构体、顺反异构体和农业和兽医可接受的盐。本发明涉及用于农业和兽医领域的杀虫用途和目的的给药和应用式I的吡啶化合物的方法。该发明还涉及式I的吡啶化合物的新衍生物。