Emetine (hydrochloride)
(Synonyms: 盐酸吐根碱) 目录号 : GC43599An alkaloid with diverse biological activities
Cas No.:316-42-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Emetine (dihydrochloride) is an anti-protozoal drug previously used for intestinal and tissue amoebiasis[1].
Emetine dihydrochloride is reported to have an IC50 value of 1 nM on the drug sensitive 3D7 P. falciparum parasite strains. Dose response curves are determined for both drugs using K1 resistant isolates and IC50 values of 47 nM and 2.6 nM established for emetine dihydrochloride hydrate and DHA, respectively[1]. After the lymphoblasts are treated with emetine dihydrochloride, the expression level of the mutant allele is elevated almost equally to the wild-type alleles by direct sequencing of the corresponding cDNA[2]. Emetine dihydrochloride is identified as a lead compound with significant concentration dependent suppression of PEDF-induced TNF secretion and an IC50 of 146 nM. Emetine dihydrochloride inhibits PEDF-mediated TNF release without affecting cell viability and binds to PEDF receptor ATGL with high-binding affinity (KD=14.3 nM)[3].Emetine dihydrochloride reduces cell viability, induces apoptosis, promptes AML cells towards differentiation and downregulates HIF-1α[4].
Emetine dihydrochloride (0.002, 0.02, 0.2 and 2 mg/kg) not only attenuates blood glucose levels in dose-dependent way but also induces a persistent attenuation of blood glucose levels. Daily administration of emetine dihydrochloride dose-dependently attenuates hyperglycemic response by d 21. Consistent with this observation, administration of emetine dihydrochloride, but not the vehicle control, results in a sustained attenuation of blood glucose levels. Emetine dihydrochloride improves disease severity in a spontaneous model of NOD T1D[3]. Emetine dihydrochloride (1 mg/kg) reduces both leukemia burden in an in vivo xenotransplantation mouse model and the clonogenic capacity of leukemic cells upon treatment[4].
References:
[1]. Matthews H, et al. Drug repositioning as a route to anti-malarial drug discovery: preliminary investigation of the in vitro anti-malarial efficacy of emetine dihydrochloride hydrate. Malar J. 2013 Oct 9;12:359.
[2]. Wu L, et al. PRRT2 truncated mutations lead to nonsense-mediated mRNA decay in Paroxysmal Kinesigenic Dyskinesia. Parkinsonism Relat Disord. 2014 Dec;20(12):1399-404
[3]. Hudson LK, et al. Emetine Di-HCl attenuates Type 1 diabetes mellitus in mice. Mol Med. 2016 Jun 10;22
[4]. Cornet-Masana JM, et al. Emetine induces chemosensitivity and reduces clonogenicity of acute myeloid leukemia cells. Oncotarget. 2016 Apr 26;7(17):23239-50
| Cas No. | 316-42-7 | SDF | |
| 别名 | 盐酸吐根碱 | ||
| 化学名 | (2S,3R,11bS)-3-ethyl-1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-2-[[(1R)-1,2,3,4-tetrahydro-6,7-dimethoxy-1-isoquinolinyl]methyl]-2H-benzo[a]quinolizine, dihydrochloride, hydrate | ||
| Canonical SMILES | CC[C@@H]1[C@@H](C[C@@]2(C3=CC(OC)=C(C=C3CCN2)OC)[H])C[C@]4(C5=CC(OC)=C(C=C5CCN4C1)OC)[H].Cl.Cl | ||
| 分子式 | C29H40N2O4 • 2HCl | 分子量 | 553.6 |
| 溶解度 | 1mg/ml in chloroform; 100mg/ml in water | 储存条件 | Store at -20°C,protect from light |
| 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 | 1.8064 mL | 9.0318 mL | 18.0636 mL |
| 5 mM | 0.3613 mL | 1.8064 mL | 3.6127 mL |
| 10 mM | 0.1806 mL | 0.9032 mL | 1.8064 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 |
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| % 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。
Antineoplastic Agents. 607. Emetine Auristatins
J Nat Prod 2020 May 22;83(5):1571-1576.PMID:32323990DOI:10.1021/acs.jnatprod.0c00031.
The remarkable biological activity of the dolastatin 10 structural modifications quinstatins and isoquinstatins prompted further investigation into drug hybrids containing biologically active isoquinoline moieties. In this study, the isoquinoline alkaloid Emetine was selected as one of the structural domains of a hybrid molecule. That was accomplished by covalently bonding the Dov-Val-Dil-Dap peptide sequence of dolastatin 10 peptide at the N-2' secondary amine of Emetine. Three new hybrids were synthesized, 5, 9, and 10. Comparison of the biological activity of these new peptide-emetine analogues with Emetine showed complete retention of activity for 5 and a 10-fold decrease for hybrids 9 and 10. The result was surprising, as the activity of Emetine is usually lost or greatly reduced when substituted at the N-2' position.
Emetine blocks DNA replication via proteosynthesis inhibition not by targeting Okazaki fragments
Life Sci Alliance 2022 Sep 9;5(12):e202201560.PMID:36260751DOI:10.26508/lsa.202201560.
DNA synthesis of the leading and lagging strands works independently and cells tolerate single-stranded DNA generated during strand uncoupling if it is protected by RPA molecules. Natural alkaloid Emetine is used as a specific inhibitor of lagging strand synthesis, uncoupling leading and lagging strand replication. Here, by analysis of lagging strand synthesis inhibitors, we show that despite Emetine completely inhibiting DNA replication: it does not induce the generation of single-stranded DNA and chromatin-bound RPA32 (CB-RPA32). In line with this, Emetine does not activate the replication checkpoint nor DNA damage response. Emetine is also an inhibitor of proteosynthesis and ongoing proteosynthesis is essential for the accurate replication of DNA. Mechanistically, we demonstrate that the acute block of proteosynthesis by Emetine temporally precedes its effects on DNA replication. Thus, our results are consistent with the hypothesis that Emetine affects DNA replication by proteosynthesis inhibition. Emetine and mild POLA1 inhibition prevent S-phase poly(ADP-ribosyl)ation. Collectively, our study reveals that Emetine is not a specific lagging strand synthesis inhibitor with implications for its use in molecular biology.
Emetine in Combination with Chloroquine Induces Oncolytic Potential of HIV-1-Based Lentiviral Particles
Cells 2022 Sep 10;11(18):2829.PMID:36139404DOI:10.3390/cells11182829.
Chloroquine and Emetine are drugs used to treat human parasitic infections. In addition, it has been shown that these drugs have an antiviral effect. Both drugs were also found to cause a suppressive effect on the growth of cancer cells of different origins. Here, using the replication-deficient HIV-1-based lentiviral vector particles, we evaluated the ability of the combination of these drugs to reduce viral transduction efficiency. We showed that these drugs act synergistically to decrease cancer cell growth when added in combination with medium containing lentiviral particles. We found that the combination of these drugs with lentiviral particles decreases the viability of treated cells. Taken together, we state the oncolytic potential of the medium containing HIV-1-based particles provoked by the combination of Chloroquine and Emetine.
Emetine protects mice from enterovirus infection by inhibiting viral translation
Antiviral Res 2020 Jan;173:104650.PMID:31734270DOI:10.1016/j.antiviral.2019.104650.
IRES-driven translation plays an essential role in picornavirus infection. However, there are seldom reports of compounds targeting this pathway with effective protection in animal models. Here, we identified Emetine, an antiprotozoal drug, which inhibits EV-A71 with an EC50 value of 0.04 μM and a CC50 value of 10 μM in RD cell culture. Interestingly, Emetine exhibits activities against a series of human enteroviruses, including CV-A16, CV-B1, EV-D68, Echov-6, etc., at the nanomolar level. When orally administered at 0.20 mg/kg twice a day in an EV-A71 mouse model, Emetine reduced viral loads in various organs and completely prevented diseases and death. A mechanistic study demonstrated that Emetine suppressed EV-A71 by inhibiting viral IRES-driven translation. Taken together, these data indicate Emetine as a promising candidate to treat picornavirus infection.
Emetine suppresses SARS-CoV-2 replication by inhibiting interaction of viral mRNA with eIF4E
Antiviral Res 2021 May;189:105056.PMID:33711336DOI:10.1016/j.antiviral.2021.105056.
Emetine is a FDA-approved drug for the treatment of amebiasis. Previously we demonstrated the antiviral efficacy of Emetine against some RNA and DNA viruses. In this study, we evaluated the in vitro antiviral efficacy of Emetine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and found it to be a low nanomolar (nM) inhibitor. Interestingly, Emetine exhibited protective efficacy against lethal challenge with infectious bronchitis virus (IBV; a chicken coronavirus) in the embryonated chicken egg infection model. Emetine treatment led to a decrease in viral RNA and protein synthesis without affecting other steps of viral life cycle such as attachment, entry and budding. In a chromatin immunoprecipitation (CHIP) assay, Emetine was shown to disrupt the binding of SARS-CoV-2 mRNA with eIF4E (eukaryotic translation initiation factor 4E, a cellular cap-binding protein required for initiation of protein translation). Further, molecular docking and molecular dynamics simulation studies suggested that Emetine may bind to the cap-binding pocket of eIF4E, in a similar conformation as m7-GTP binds. Additionally, SARS-CoV-2 was shown to exploit ERK/MNK1/eIF4E signalling pathway for its effective replication in the target cells. Collectively our results suggest that further detailed evaluation of Emetine as a potential treatment for COVID-19 may be warranted.