规格 | 价格 | 库存 | 数量 |
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10 mM * 1 mL in DMSO |
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5mg |
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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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500mg |
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1g |
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2g |
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Other Sizes |
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靶点 |
OCT1 (IC50 = 36.8 μM); OCT2 (IC50 = 1852.6 μM)
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体外研究 (In Vitro) |
野百合碱是一种天然存在的配体,具有很强的抗肿瘤作用和剂量依赖性细胞毒性。在 HepG2 细胞上测试时,野百合碱的 IC50 为 24.966 µg/mL,体外遗传毒性为 IC50 的 2 倍 [2]。
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体内研究 (In Vivo) |
高血压大鼠模型可以通过使用野百合碱的动物建模来创建。在大鼠中,MCT 会导致肺血管综合征,其典型表现为肺心病、肺动脉高压 (PH) 和增殖性肺血管炎 [3]。野百合碱诱导的动物模型的优点是与临床前模型中人类肺动脉高压(PAH)的几个重要方面非常相似,例如血管重塑、平滑肌细胞增殖、内皮功能障碍、炎症细胞因子上调和右心室衰竭。 [4]。野百合碱的施用导致与外周出血(PH)发病机制相关的多个途径发生改变,例如刺激糖酵解、增殖标记物升高、肉碱稳态紊乱、炎症和纤维化生物标记物升高以及谷胱甘肽产生。减少[5]。给予单剂量野百合碱(60 mg/kg ip)的大鼠肺动脉压力显着升高,右心室肥厚和肺动脉结构重塑也增加。然后,给予黄芪甲苷 IV (ASIV),剂量为 10 和 30 mg/kg/d,持续 21 天。通过增强肺动脉重塑和炎症,ASIV可以预防肺动脉高压[7]。野百合碱(60 mg/kg;腹腔注射;单剂量)3-4 周后诱导大鼠肺动脉高压 (PAH) 模型 [7]。在左肺切除大鼠模型中,野百合碱(60 mg/kg;腹腔注射;单剂量)表现出显着的抗肿瘤功效以及剂量依赖性细胞毒性[9]。使用 1 N HCl 溶解野百合碱,然后用无菌盐水稀释,并使用 1 N NaOH 将 pH 调至 7.4 [7]。
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酶活实验 |
本研究利用体外稳定转染的HEK293细胞,系统地研究了山莨菪碱和野百合碱两种生物碱与有机阳离子转运蛋白OCT1、2、3、MATE1和MATE2-K的相互作用。山莨菪碱和野百合碱均抑制OCTs和MATE转运蛋白。对OCT1的最低IC50为12.9µmol·L-1的山莨菪碱,对OCT2的最高IC50为1.8 mmol·L-1野百合碱。Anisodine是OCT2的底物(Km=13.3±2.6µmol·L-1和Vmax=286.8±53.6 pmol/mg蛋白质/min)。Monocrotaline被确定为OCT1(Km=109.1±17.8µmol·L-1,Vmax=576.5±87.5 pmol/mg蛋白质/min)和OCT2(Km=64.7±14.8µmol•L-1,V max=180.7±22.0 pmol/mg蛋白/min)的底物,而不是OCT3和MATE转运蛋白。结果表明,OCT2可能对肾清除山莨菪碱很重要,OCT1负责野百合碱进入肝脏。然而,MATE1和MATE2-K都不能促进山莨菪碱和野百合碱的跨细胞转运。这些药物可能会在高OCT1表达(肝脏)和高OCT2表达(肾脏)的器官中积聚[8]。
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细胞实验 |
细胞活力测定[2]
细胞类型: HepG2 细胞 测试浓度: 25、50、100 和 200 µg/mL 孵育时间:48小时 实验结果:诱导凋亡率呈剂量依赖性。 |
动物实验 |
Astragaloside IV blocks monocrotaline‑induced pulmonary arterial hypertension by improving inflammation and pulmonary artery remodeling[7]
Male Sprague-Dawley rats, 8 weeks old weighing 200-230 g, were obtained from the Animal Center of Qiqihar Medical University. The protocol for the present study was approved by the Qiqihar Medical University Institutional Review Board (no. QMU-AECC-2018-27). The rats were housed in a temperature- and humidity-controlled environment with 12-h light/dark cycles. Food and water were available ad libitum. The experiments conformed to the National Institutes of Health guidelines concerning the care and use of laboratory animals, and all animal procedures were approved by the Animal Care and Use Committee of the Qiqihar Medical University. The rats were randomly assigned to 4 groups (8 rats per group) as follows: The control group, the monocrotaline (MCT) group, the MCT + 10 mg/kg/dahy ASIV (ASIV10) group, and the MCT + 30 mg/kg/day ASIV (ASIV30) group. To establish MCT-induced PAH, the rats were administered a single intraperitoneal injection of MCT (60 mg/kg), while the control group received the same volume of saline. MCT was dissolved in 1 N HCl, diluted in sterile saline and adjusted to pH 7.4 with 1 N NaOH. ASIV was initially dissolved in DMSO as a stock solution and further diluted in saline immediately prior to use; the final DMSO concentration was 0.5%. Within hours of the MCT injection, there were signs of pulmonary vascular endothelial damage, but without an increase in pulmonary artery pressure. By 2 weeks, pulmonary artery pressure began to increase, as previously described. At 2 days following the MCT administration, ASIV or the vehicle (0.5% DMSO in saline) were administered intraperitoneally once a day for 21 days. A total of 36 male specific-pathogen free Sprague-Dawley rats (age, 6–8 weeks; weight, 300–350 g) were kept in a conventional room at 22±2°C, a relative humidity of 55±10% and a 12-h light/dark cycle. Rats had access to food and water ad libitum. The rats were divided into the following three equal groups at random: Control group, where rats received no treatment; model group, where rats underwent a left pneumonectomy plus subcutaneous injection of 60 mg/kg monocrotaline (MCT), a natural ligand exhibiting dose-dependent cytotoxicity with potent antineoplastic activity, at 7 days following the procedure; PTX group, where rats underwent the same procedure as those in the model group plus administration of 2 mg/kg PTX via the caudal vein (21) daily for 1 week at 3 weeks following injection of MCT[9]. |
参考文献 |
[1]. The monocrotaline model of pulmonary hypertension in perspective. Am J Physiol Lung Cell Mol Physiol. 2012 Feb 15;302(4):L363-9.
[2]. Antineoplastic activity of monocrotaline against hepatocellular carcinoma. Anticancer Agents Med Chem. 2014;14(9):1237-48. [3]. Mechanisms and pathology of monocrotaline pulmonary toxicity. Crit Rev Toxicol. 1992;22(5-6):307-25. [4]. Exploring the monocrotaline animal model for the study of pulmonary arterial hypertension: A network approach. Pulm Pharmacol Ther. 2015 Dec;35:8-16. [5]. Metabolic Changes Precede the Development of Pulmonary Hypertension in the Monocrotaline Exposed RatLung. PLoS One. 2016 Mar 3;11(3):e0150480. [6]. Experimental animal models of pulmonary hypertension: Development and challenges. Animal Model Exp Med. 2022 Sep; 5(3):207-216. [7]. Astragaloside IV blocks monocrotaline‑induced pulmonary arterial hypertension by improving inflammation and pulmonary artery remodeling. Int J Mol Med. 2021 Feb;47(2):595-606. [8]. An in vitro study on interaction of anisodine and monocrotaline with organic cation transporters of the SLC22 and SLC47 families. Chin J Nat Med. 2019 Jul;17(7):490-497. [9]. Effects of paclitaxel intervention on pulmonary vascular remodeling in rats with pulmonary hypertension. Exp Ther Med. 2019 Feb;17(2):1163-1170. |
其他信息 |
Monocrotaline is a pyrrolizidine alkaloid.
Monocrotaline can cause cancer according to an independent committee of scientific and health experts. A pyrrolizidine alkaloid and a toxic plant constituent that poisons livestock and humans through the ingestion of contaminated grains and other foods. The alkaloid causes pulmonary artery hypertension, right ventricular hypertrophy, and pathological changes in the pulmonary vasculature. Significant attenuation of the cardiopulmonary changes are noted after oral magnesium treatment. Therapeutic Uses /Exptl Ther/ Antitumor effects of 22 pyrrolizidine alkaloids and derivatives were studied in mice with adenocarcinomas 755, l-1210 leukemia or sarcoma 180, rats with im or sc walker 256 carcinomasarcoma and in kb carcinoma cell cultures; 1 compound each was also tested in mice with ascites ehrlich carcinoma and hamsters with plasmacytoma number 1. Significant activity against the solid tumors, by CCNSC standards (58% or more decrease in tumor size), was seen with monocrotaline (NSC-28693) in 3 of the above tumors and in p-1. Monocrotaline n-oxide was without significant activity in any of the systems tested. View More
Absorption, Distribution and Excretion Metabolism / Metabolites Studies with monocrotaline have confirmed the formation of pyrrolic metabolites by the mixed-function oxidase system of the microsomal fraction of rat liver. Dehydromonocrotaline (monocrotaline pyrrole) is highly cytotoxic, producing pulmonary, cardiac, vascular and hepatic lesions similar to those produced by the parent alkaloid. It is a highly reactive alkylating agent which, on formation within the cell, reacts immediately with cell constituents to give soluble or bound secondary metabolites or hydrolyzes to the dehydroaminoalcohol, dehydroretronecine. IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V10 295 (1976) Hazardous Substances Data Bank (HSDB) Using microsomes from livers of phenobarbital-pretreated male rats, all 13 alkaloids tested were metabolized to n-oxide and pyrrole formation. The 2 pathways appeared to be independent. Ratio of n-oxide to pyrrolic metabolites varied, depending on type of ester: it was highest for open diester alkaloids and lowest for 12-membered macrocyclic diesters and for monoesters. Monocrotaline was one of those tested. PMID:6825198 MATTOCKS AR, BIRD I; CHEM-BIOL INTERACT 43 (2): 209 (1983) Mechanism of Action The toxicology of monocrotaline is complex, and the mechanisms by which it causes lung injury, pulmonary hypertension, and right heart enlargement have remained elusive. ... Monocrotaline is bioactivated by the liver to a reactive, electrophilic pyrrole that travels via the circulation to the lung, where injury results. When low, iv doses of monocrotaline pyrrole are given to rats, a delay of several days occurs before lung injury and pulmonary hypertension become apparent. Moderate depletion of blood platelets around the time of the onset of lung injury lessens the subsequent development of right ventricular enlargement, suggesting a reduction in the pulmonary hypertensive response to monocrotaline pyrrole. This observation prompted a study of the role of platelet-derived mediators in the cardiopulmonary response to monocrotaline pyrrole. A stable analog of thromboxane A2(TxA2) caused a greater increase in right ventricular pressure in monocrotaline pyrrole treated rats compared to controls, and lungs isolated from monocrotaline pyrrole treated rats produced more TxB2 than those of controls. However, administration of drugs that either inhibited thromboxane synthesis or antagonized the effects of thromboxane did not afford protection from monocrotaline pyrrole in vivo. Serotonin, another vasoactive mediator released by platelets, caused an exaggerated vasoconstrictor response in isolated lungs from rats treated with monocrotaline pyrrole. Moreover, removal and inactivation of circulating serotonin by the pulmonary vasculature was impaired by treatment of rats with monocrotaline pyrrole. However, administration of serotonin receptor antagonists did not attenuate the cardiopulmonary effects of monocrotaline pyrrole in vivo. These results suggest that neither TxA2 nor serotonin is the sole mediator of the pneumotoxicity due to monocrotaline pyrrole. Thus, the mechanism by which platelets are involved in the pathogenesis of the pneumotoxic response to monocrotaline pyrrole remains an unsolved puzzle. PMID:3130680 Roth RA, Ganey PE; Toxicol Appl Pharmacol 93 (3): 463-71 (1988) Sources/Uses Toxic pyrrolizidine alkaloid from Crotalaria spp; Used to induce lung diseases in rats; [Merck Index] Used in parts of Africa and India in traditional medicine; [HSDB] Merck Index - O'Neil MJ, Heckelman PE, Dobbelaar PH, Roman KJ (eds). The Merck Index, An Encyclopedia of Chemicals, Drugs, and Biologicals, 15th Ed. Cambridge, UK: The Royal Society of Chemistry, 2013. Haz-Map, Information on Hazardous Chemicals and Occupational Diseases C. retusa /which contains monocrotaline/ has been widely used as a dye plant and possibly as a vegetable in some parts of East Africa. In West Africa the root is crushed and mixed with spices as a colic remedy, and a decoction of the leaf, or sometimes the fresh juice of the plant, is taken for the relief of fever. In India, the root has been used as a remedy for hemoptysis, the leaf as a vegetable and a preparation of the plant as a local application in skin diseases. IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V10 292 (1976) Clinical Laboratory Methods The rapid and sensitive identification and quantification of important pyrrolizidine alkaloid metabolites using tandem mass spectrometry (MS/MS) and GC/MS is described. Identifications of N-oxide and hydrolytic metabolites of the pyrrolizidine alkaloids senecionine and monocrotaline in extracts of mouse hepatic microsomal incubations were accomplished by comparing collisionally activated decomp/mass-analyzed ion kinetic energy spectra of specific ions from microsomal extracts with spectra obtained from synthetic stds. of suspected metabolites. Trace amt of the toxic metabolite dihydropyrrolizine were observed by GC/MS of trimethylsilyl deriv, but the amt present in hepatic microsomal extracts were below the MS/MS limit of detection. Quant detn of senecionine N-oxide were performed by fast atom bombardment MS/MS. Suppression of N-oxide ionization by other substances in the extracts was judged to be minimal. The trimethylsilyl deriv of the metabolites senecic acid, monocrotalic acid, and dihydropyrrolizine were quantified using capillary GC/MS. The relative contributions of the 3 major pathways of pyrrolizidine alkaloid metab. (N-oxidn, hydrolysis, and oxidn to pyrrolic cmpd) can be assessed using a single analysis instrument and minimal sample prepn. PMID:3365497 Winter CK et al; Biomed Environ Mass Spectrom 15 (5): 265-73 (1988) |
分子式 |
C16H23NO6
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分子量 |
325.36
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精确质量 |
325.152
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元素分析 |
C, 59.07; H, 7.13; N, 4.31; O, 29.50
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CAS号 |
315-22-0
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外观&性状 |
Typically exists as white to off-white solids at room temperature
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密度 |
1.4±0.1 g/cm3
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沸点 |
537.3±50.0 °C at 760 mmHg
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熔点 |
204ºC (dec.)(lit.)
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闪点 |
278.7±30.1 °C
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蒸汽压 |
0.0±3.2 mmHg at 25°C
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折射率 |
1.586
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LogP |
-0.37
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tPSA |
96.3
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SMILES |
O=C(O[C@]1([H])CCN2[C@]1([H])C(CO3)=CC2)[C@H](C)[C@@](C)(O)[C@@](C)(O)C3=O
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InChi Key |
QVCMHGGNRFRMAD-XFGHUUIASA-N
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InChi Code |
InChI=1S/C16H23NO6/c1-9-13(18)23-11-5-7-17-6-4-10(12(11)17)8-22-14(19)16(3,21)15(9,2)20/h4,9,11-12,20-21H,5-8H2,1-3H3/t9-,11+,12+,15+,16-/m0/s1
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化学名 |
20-Norcrotalanan-11,15-dione, 14,19-dihydro-12,13-dihydroxy-, (13-alpha,14-alpha)- (9CI)
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别名 |
NSC 28693; NSC-28693; monocrotaline; Crotaline; 315-22-0; Monocrotalin; (-)-Monocrotaline; CHEBI:6980; Retronecine cyclic 2,3-dihydroxy-2,3,4-trimethylglutarate; (13-alpha,14-alpha)-14,19-Dihydro-12,13-dihydroxy-20-norcrotalanan-11,15-dione; NSC28693
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HS Tariff Code |
2934.99.9001
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存储方式 |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
运输条件 |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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溶解度 (体外实验) |
1M HCl : 200 mg/mL (~614.70 mM)
DMSO : ~25 mg/mL (~76.84 mM) H2O : ~2 mg/mL (~6.15 mM) |
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溶解度 (体内实验) |
配方 1 中的溶解度: ≥ 2.5 mg/mL (7.68 mM) (饱和度未知) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (这些助溶剂从左到右依次添加,逐一添加), 澄清溶液。
*生理盐水的制备:将 0.9 g 氯化钠溶解在 100 mL ddH₂O中,得到澄清溶液。 配方 2 中的溶解度: ≥ 2.5 mg/mL (7.68 mM) (饱和度未知) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加,逐一添加), 悬浮液。 *20% SBE-β-CD 生理盐水溶液的制备(4°C,1 周):将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中,得到澄清溶液。 View More
配方 3 中的溶解度: ≥ 2.08 mg/mL (6.39 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加,逐一添加), 澄清溶液。 配方 4 中的溶解度: ≥ 2.08 mg/mL (6.39 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加,逐一添加), 澄清溶液。 例如,若需制备1 mL的工作液,可将100μL 20.8mg/mL澄清的DMSO储备液加入到900μL 20%SBE-β-CD生理盐水中,混匀。 *20% SBE-β-CD 生理盐水溶液的制备(4°C,1 周):将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中,得到澄清溶液。 配方 5 中的溶解度: ≥ 2.08 mg/mL (6.39 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加,逐一添加), 澄清溶液。 例如,若需制备1 mL的工作液,可将100 μL 20.8 mg/mL 澄清 DMSO 储备液加入900 μL 玉米油中,混合均匀。 配方 6 中的溶解度: ≥ 0.5 mg/mL (1.54 mM)(饱和度未知) in 1% DMSO 99% Saline (这些助溶剂从左到右依次添加,逐一添加), 澄清溶液。 配方 7 中的溶解度: 4.17 mg/mL (12.82 mM) in PBS (这些助溶剂从左到右依次添加,逐一添加), 澄清溶液; 超声助溶 (<60°C). 配方 8 中的溶解度: 21 mg/mL (64.54 mM) in 20% HP-β-CD in Saline (这些助溶剂从左到右依次添加,逐一添加), 澄清溶液; 需要超声波和加温并加热至 53°C。 *生理盐水的制备:将 0.9 g 氯化钠溶解在 100 mL ddH₂O中,得到澄清溶液。 1、请先配制澄清的储备液(如:用DMSO配置50 或 100 mg/mL母液(储备液)); 2、取适量母液,按从左到右的顺序依次添加助溶剂,澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明,并不一定代表此产品 的实际溶解配方): 10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline); 假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀/澄清;向上述体系中加入50 μL Tween-80,混合均匀/澄清;然后继续加入450 μL ddH2O (或 saline)定容至 1 mL; 3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例; 4、 如产品在配制过程中出现沉淀/析出,可通过加热(≤50℃)或超声的方式助溶; 5、为保证最佳实验结果,工作液请现配现用! 6、如不确定怎么将母液配置成体内动物实验的工作液,请查看说明书或联系我们; 7、 以上所有助溶剂都可在 Invivochem.cn网站购买。 |
制备储备液 | 1 mg | 5 mg | 10 mg | |
1 mM | 3.0735 mL | 15.3676 mL | 30.7352 mL | |
5 mM | 0.6147 mL | 3.0735 mL | 6.1470 mL | |
10 mM | 0.3074 mL | 1.5368 mL | 3.0735 mL |
1、根据实验需要选择合适的溶剂配制储备液 (母液):对于大多数产品,InvivoChem推荐用DMSO配置母液 (比如:5、10、20mM或者10、20、50 mg/mL浓度),个别水溶性高的产品可直接溶于水。产品在DMSO 、水或其他溶剂中的具体溶解度详见上”溶解度 (体外)”部分;
2、如果您找不到您想要的溶解度信息,或者很难将产品溶解在溶液中,请联系我们;
3、建议使用下列计算器进行相关计算(摩尔浓度计算器、稀释计算器、分子量计算器、重组计算器等);
4、母液配好之后,将其分装到常规用量,并储存在-20°C或-80°C,尽量减少反复冻融循环。
计算结果:
工作液浓度: mg/mL;
DMSO母液配制方法: mg 药物溶于 μL DMSO溶液(母液浓度 mg/mL)。如该浓度超过该批次药物DMSO溶解度,请首先与我们联系。
体内配方配制方法:取 μL DMSO母液,加入 μL PEG300,混匀澄清后加入μL Tween 80,混匀澄清后加入 μL ddH2O,混匀澄清。
(1) 请确保溶液澄清之后,再加入下一种溶剂 (助溶剂) 。可利用涡旋、超声或水浴加热等方法助溶;
(2) 一定要按顺序加入溶剂 (助溶剂) 。