Cobomarsen
(Synonyms: MRG-106) 目录号 : GC64498
Cobomarsen (MRG-106) 是 miR-155 的寡核苷酸抑制剂。 Cobomarsen 抑制与细胞存活相关的多种基因通路 (JAK/STAT，MAPK/ERK 和 PI3K/AKT)。Cobomarsen 可用于 B 细胞淋巴瘤的研究。
Cas No.:1848257-52-2
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
Cobomarsen (MRG-106) is an oligonucleotide inhibitor of miR-155. Cobomarsen inhibits multiple gene pathways associated with cell survival (including JAK/STAT, MAPK/ERK and PI3K/AKT). Cobomarsen can be used for the research of B-cell lymphoma[1][2].
Cobomarsen (10 μM; 48-96 h) reduces cell proliferation and induces apoptosis in U2932, OCI-LY3, and RCK8 cells[2].Cobomarsen (10 μM; 72 h) significantly increases the expression of the four direct targets in the cell lines that overexpress miR-155[1].Cobomarsen (10 μM; 12 days) reduces cellular proliferation and induces apoptosis in MF and HTLV-1+ CTCL cells[1].Cobomarsen (10-50 μM; 7 days) reduces phosphorylation of the downstream signalling proteins AKT, ERK1/2, and STAT-3 in primary human activated T cells or MF cell lines[1].
Cobomarsen (1 mg/kg; i.v. on days 0, 2, 4, and 7) inhibits tumor growth in mice carrying U2932 cells xenografts[2].
[1]. Seto AG, et, al. Cobomarsen, an oligonucleotide inhibitor of miR-155, co-ordinately regulates multiple survival pathways to reduce cellular proliferation and survival in cutaneous T-cell lymphoma. Br J Haematol. 2018 Nov;183(3):428-444.
[2]. Anastasiadou E, et, al. Cobomarsen, an Oligonucleotide Inhibitor of miR-155, Slows DLBCL Tumor Cell Growth In Vitro and In Vivo. Clin Cancer Res. 2021 Feb 15;27(4):1139-1149.
| Cas No. | 1848257-52-2 | SDF | Download SDF |
| 别名 | MRG-106 | ||
| 分子式 | 分子量 | 4736 | |
| 溶解度 | 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 | 0.2111 mL | 1.0557 mL | 2.1115 mL |
| 5 mM | 0.0422 mL | 0.2111 mL | 0.4223 mL |
| 10 mM | 0.0211 mL | 0.1056 mL | 0.2111 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。
Cobomarsen, an Oligonucleotide Inhibitor of miR-155, Slows DLBCL Tumor Cell Growth In Vitro and In Vivo
Clin Cancer Res 2021 Feb 15;27(4):1139-1149.PMID:33208342DOI:10.1158/1078-0432.CCR-20-3139.
Purpose: miRNA-155 is an oncogenic miRNA highly expressed in B-cell malignancies, particularly in the non-germinal center B-cell or activated B-cell subtype of diffuse large B-cell lymphoma (ABC-DLBCL), where it is considered a potential diagnostic and prognostic biomarker. Thus, miR-155 inhibition represents an important therapeutic strategy for B-cell lymphomas. In this study, we tested the efficacy and pharmacodynamic activity of an oligonucleotide inhibitor of miR-155, Cobomarsen, in ABC-DLBCL cell lines and in corresponding xenograft mouse models. In addition, we assessed the therapeutic efficacy and safety of Cobomarsen in a patient diagnosed with aggressive ABC-DLBCL. Experimental design: Preclinical studies included the delivery of Cobomarsen to highly miR-155-expressing ABC-DLBCL cell lines to assess any phenotypic changes, as well as intravenous injections of Cobomarsen in NSG mice carrying ABC-DLBCL xenografts, to study tumor growth and pharmacodynamics of the compound over time. To begin to test its safety and therapeutic efficacy, a patient was recruited who underwent five cycles of Cobomarsen treatment. Results: Cobomarsen decreased cell proliferation and induced apoptosis in ABC-DLBCL cell lines. Intravenous administration of Cobomarsen in a xenograft NSG mouse model of ABC-DLBCL reduced tumor volume, triggered apoptosis, and derepressed direct miR-155 target genes. Finally, the compound reduced and stabilized tumor growth without any toxic effects for the patient. Conclusions: Our findings support the potential therapeutic application of Cobomarsen in ABC-DLBCL and other types of lymphoma with elevated miR-155 expression.
Cobomarsen, an oligonucleotide inhibitor of miR-155, co-ordinately regulates multiple survival pathways to reduce cellular proliferation and survival in cutaneous T-cell lymphoma
Br J Haematol 2018 Nov;183(3):428-444.PMID:30125933DOI:10.1111/bjh.15547.
miR-155, a microRNA associated with poor prognosis in lymphoma and leukaemia, has been implicated in the progression of mycosis fungoides (MF), the most common form of cutaneous T-cell lymphoma (CTCL). In this study, we developed and tested Cobomarsen (MRG-106), a locked nucleic acid-modified oligonucleotide inhibitor of miR-155. In MF and human lymphotropic virus type 1 (HTLV-1+) CTCL cell lines in vitro, inhibition of miR-155 with Cobomarsen de-repressed direct miR-155 targets, decreased expression of multiple gene pathways associated with cell survival, reduced survival signalling, decreased cell proliferation and activated apoptosis. We identified a set of genes that are significantly regulated by Cobomarsen, including direct and downstream targets of miR-155. Using clinical biopsies from MF patients, we demonstrated that expression of these pharmacodynamic biomarkers is dysregulated in MF and associated with miR-155 expression level and MF lesion severity. Further, we demonstrated that miR-155 simultaneously regulates multiple parallel survival pathways (including JAK/STAT, MAPK/ERK and PI3K/AKT) previously associated with the pathogenesis of MF, and that these survival pathways are inhibited by Cobomarsen in vitro. A first-in-human phase 1 clinical trial of Cobomarsen in patients with CTCL is currently underway, in which the panel of proposed biomarkers will be leveraged to assess pharmacodynamic response to Cobomarsen therapy.
miR-155 as a novel clinical target for hematological malignancies
Carcinogenesis 2020 Mar 13;41(1):2-7.PMID:31711135DOI:10.1093/carcin/bgz183.
MicroRNAs (miRNAs), small non-coding RNAs that repress target genes, are a promising new focus of targeted therapeutics for cancer. miR-155 is a well-studied miRNA involved in inflammation that acts oncogenically in many hematological malignancies. Like other miRNAs, its role in these diseases is complex and nuanced, which gives particular power to its inhibition in diseased cells. This, together with increasing understanding of its key targets in cancer and the use of powerful mouse models of miR-155 in cancer, makes miR-155 an ideal target for therapeutic inhibition. Here, we review the role of miRNAs, and particularly miR-155, in cancers, and discuss progress on therapeutically targeting it, including the ongoing clinical trial of anti-miR-155 molecule Cobomarsen (MRG-106).