Ikarugamycin
(Synonyms: 斑鸠霉素) 目录号 : GC43892
An antiprotozoan antibiotic
Cas No.:36531-78-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Ikarugamycin is a macrocyclic antibiotic first isolated from Streptomyces sp. that demonstrates potent antiprotozoal activity.[1] It exhibits cytotoxic effects in cancer cell lines, inhibiting cell proliferation (IC50 = 221.3 nM in HL-60 cells) through genotoxicity and by inducing apoptosis and activation of caspases.[2] It also was shown to significantly inhibit oxidized low-density lipoprotein-induced accumulation of cholesteryl esters in macrophages at 1-4 μM.[3] Additionally, ikarugamycin is used to inhibit clathrin-coated pit-mediated endocytosis.[4]
Reference:
[1]. Jomon, K., Kuroda, Y., Ajisaka, M., et al. A new antibiotic, ikarugamycin. J.Antibiot.(Tokyo) 25(5), 271-280 (1972).
[2]. Popescu, R., Heiss, E.H., Ferk, F., et al. Ikarugamycin induces DNA damage, intracellular calcium increase, p38 MAP kinase activation and apoptosis in HL-60 human promyelocytic leukemia cells. Mutation Research 709-710, 60-66 (2011).
[3]. Hasumi, K., Shinohara, C., Naganuma, S., et al. Inhibition of the uptake of oxidized low-density lipoprotein in macrophage J774 by the antibiotic ikarugamycin. European Journal of Biochemistry 205(2), 841-846 (1992).
[4]. Luo, T., Fredericksen, B.L., Hasumi, K., et al. Human immunodeficiency virus type 1 Nef-induced CD4 cell surface downregulation is inhibited by ikarugamycin. Journal of Virology 75(5), 2488-2492 (2001).
| Cas No. | 36531-78-9 | SDF | |
| 别名 | 斑鸠霉素 | ||
| 化学名 | (2R,3R,7Z,14S,19E)-3-ethyl-2,3,3aS,5aR,5bS,6,10,11,12,13,14,15,20aS,21,21aR,21bR-hexadecahydro-22-hydroxy-2-methyl-14,17-metheno-17H-as-indaceno[3,2-k][1,6]diazacycloheptadecine-9,16,18(1H)-trione | ||
| Canonical SMILES | O=C(C1=C(O)[C@H](CCCN2)NC1=O)/C=C/[C@@H]3C[C@@]4([H])[C@@](C=C[C@]5([H])[C@]4([H])C[C@@H](C)[C@H]5CC)([H])[C@H]3C/C=C\C2=O | ||
| 分子式 | C29H38N2O4 | 分子量 | 478.6 |
| 溶解度 | Soluble in DMSO，DMF, slightly in ethanol, methanol | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.0894 mL | 10.4471 mL | 20.8943 mL |
| 5 mM | 0.4179 mL | 2.0894 mL | 4.1789 mL |
| 10 mM | 0.2089 mL | 1.0447 mL | 2.0894 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
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，
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 saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
A potent endocytosis inhibitor Ikarugamycin up-regulates TNF production
Biochem Biophys Rep 2021 Jul 8;27:101065.PMID:34286109DOI:10.1016/j.bbrep.2021.101065.
Ikarugamycin (IK) is an antibiotic which has been reported to have a variety of functions, such as inhibition of clathrin-mediated endocytosis (CME), anti-tumor effects and regulation of the immune system. Whether IK influences cytokine production is poorly understood. We have investigated the relationship between IK and production of tumor necrosis factor-α (TNF). TNF plays a pivotal role in pathogenesis of many diseases. Although the dynamics of soluble TNF (sTNF) has been widely explored so far, the functions of the membrane form of TNF (mTNF) have not been fully elucidated. We demonstrated that IK increases the amount of mTNF and prolongs the duration of TNF expression. This effect is unrelated to the shedding activity of disintegrin and metalloproteinase domain-containing protein 17 (ADAM 17). Our results revealed that there is a mechanism to terminate inflammation at the cellular level which IK dysregulates. Furthermore, IK can be a tool to study TNF signaling due to its effect of increasing mTNF expression.
Ikarugamycin inhibits pancreatic cancer cell glycolysis by targeting hexokinase 2
FASEB J 2020 Mar;34(3):3943-3955.PMID:31944405DOI:10.1096/fj.201901237R.
Mangrove-derived actinobacteria strains are well-known for producing novel secondary metabolites. The polycyclic tetramate macrolactam (PTM), Ikarugamycin (IKA) isolated from Streptomyces xiamenensis 318, exhibits antiproliferative activities against pancreatic ductal adenocarcinoma (PDAC) in vitro. However, the protein target for bioactive IKA is unclear. In this study, whole transcriptome-based profiling revealed that the glycolysis pathway is significantly affected by IKA. Metabolomic studies demonstrated that IKA treatment induces a significant drop in glucose-6-phosphate and a slight increase in intracellular glucose level. Analysis of glucose consumption, lactate production, and the extracellular acidification rate confirmed the inhibitory role of IKA on the glycolytic flux in PDAC cells. Surface plasmon resonance (SPR) experiments and docking studies identified the key enzyme of glycolysis, hexokinase 2 (HK2), as a molecular target of IKA. Moreover, IKA reduced tumor size without overt cytotoxicity in mice with PDAC xenografts and increased chemotherapy response to gemcitabine in PDAC cells in vitro. Taken together, IKA can block glycolysis in pancreatic cancer by targeting HK2, which may be a potential drug candidate for PDAC treatment.
Ikarugamycin: A Natural Product Inhibitor of Clathrin-Mediated Endocytosis
Traffic 2016 Oct;17(10):1139-49.PMID:27392092DOI:10.1111/tra.12425.
Ikarugamycin (IKA) is a previously discovered antibiotic, which has been shown to inhibit the uptake of oxidized low-density lipoproteins in macrophages. Furthermore, several groups have previously used IKA to inhibit clathrin-mediated endocytosis (CME) in plant cell lines. However, detailed characterization of IKA has yet to be performed. Consequently, we performed biochemistry and microscopy experiments to further characterize the effects of IKA on CME. We show that IKA has an IC50 of 2.7 μm in H1299 cells and acutely inhibits CME, but not other endocytic pathways, in a panel of cell lines. Although long-term incubation with IKA has cytotoxic effects, the short-term inhibitory effects on CME are reversible. Thus, IKA can be a useful tool for probing routes of endocytic trafficking.
Biocatalytic Total Synthesis of Ikarugamycin
Angew Chem Int Ed Engl 2017 Apr 3;56(15):4351-4355.PMID:28128495DOI:10.1002/anie.201611063.
Nature provides an inexhaustible diversity of small organic molecules with beautiful molecular architectures that have strong and selective inhibitory activities. However, this tremendous biomedical potential often remains inaccessible, as the structural complexity of natural products can render their synthetic preparation extremely challenging. This problem is addressable by harnessing the biocatalytic procedures evolved by nature. In this work, we present an enzymatic total synthesis of Ikarugamycin. The use of an iterative PKS/NRPS machinery and two reductases has allowed the construction of 15 carbon-carbon and 2 carbon-nitrogen bonds in a biocatalytic one-pot reaction. By scaling-up this method we demonstrate the applicability of biocatalytic approaches for the ex vivo synthesis of complex natural products.
New Ikarugamycin derivatives with antifungal and antibacterial properties from Streptomyces zhaozhouensis
Mar Drugs 2014 Dec 29;13(1):128-40.PMID:25551780DOI:10.3390/md13010128.
A bioassay guided fractionation of the ethyl acetate extract from culture broths of the strain Streptomyces zhaozhouensis CA-185989 led to the isolation of three new polycyclic tetramic acid macrolactams (1-3) and four known compounds. All the new compounds were structurally related to the known Streptomyces metabolite Ikarugamycin (4). Their structural elucidation was accomplished using a combination of electrospray-time of flight mass spectrometry (ESI-TOF MS) and 1D and 2D NMR analyses. Compounds 1-3 showed antifungal activity against Aspergillus fumigatus, Candida albicans and antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA).