Rituximab (Anti-Human CD20 type I, Chimeric Antibody)
(Synonyms: 利妥昔单抗; Anti-Human CD20 type I, Chimeric Antibody) 目录号 : GC34209
Rituximab is a human/murine, chimeric anti-CD20 monoclonal antibody with established efficacy, and a favorable and well-defined safety profile in patients with various CD20-expressing lymphoid malignancies[1].
Cas No.:174722-31-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
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Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
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Cell lines |
Peripheral blood mononuclear cells from B-CLL patients |
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Preparation Method |
7×104 cells/well were plated in quadruplicate in 96-well plates in the presence or absence of 0.3-1µg/ml fludarabine. After 24 h, human serum was added to a final 25% in the presence or absence of 10 µg/ml rituximab and the cells incubated for 4 h at 37°C. |
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Reaction Conditions |
10 µg/ml for 4 hours |
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Applications |
In CLL 4, rituximab and complement alone induced 34% cell death. |
| Animal experiment [2]: | |
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Animal models |
Male C57BL/6 mice, weighing 18-22 g, |
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Preparation Method |
Each animal received a single injection of rituximab (10 mg/mL) by either IV (1 and 40 mg/kg; tail vein) or SC routes (1, 10 and 40 mg/kg; mid back or mid abdomen). The volume of injection was 4 mL/kg (80 µL for 20 g mouse), and the commercially available formulation (10 mg/mL) was diluted with sterile normal saline for low doses. |
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Dosage form |
IV for 1, 40 mg/kg and SC for 1, 10, 40 mg/kg |
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Applications |
The Subcutaneous (SC) absorption of rituximab in mice shows at both tested injection sites (back and abdomen), the extent of absorption was inversely related to the dose level, the absorption of rituximab from the abdomen was faster than at the back. |
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References: [1]: Di Gaetano, N. et al. Synergism between fludarabine and rituximab revealed in a follicular lymphoma cell line resistant to the, cytotoxic activity of either drug alone. Br. J. Haematology 114, 800-809 (2001). | |
Rituximab is a human/murine, chimeric anti-CD20 monoclonal antibody with established efficacy, and a favorable and well-defined safety profile in patients with various CD20-expressing lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin lymphoma [1].
Intravenously administered rituximab was granted regulatory approval in 1997 by the US Food and Drug Administration and in 1998 by the European Medicines Agency for use in relapsed/refractory indolent non-Hodgkin lymphomas. Approvals for use in chronic lymphocytic leukemia followed in 2009 and 2010, respectively [1].
Rituximab binds with high affinity and specificity to the CD20 antigen, which is expressed on the vast majority of malignant B cells. The apparent affinity constant of rituximab for human CD20, as determined by Scatchard analysis using a human lymphoblastoid cell line, is approximately 5.2 nmol/L [2]. Rituximab provides significant, clinically meaningful benefits to patients with active rheumatoid arthritis also. In patients with active rheumatoid arthritis despite methotrexate treatment, a single course of two infusions of rituximab, alone or in combination with either cyclophosphamide or continued methotrexate, provided significant improvement in disease symptoms at both weeks 24 and 48 [3].
利妥昔单抗(Rituximab)是一种人/鼠嵌合型抗CD20单克隆抗体,已在表达各种CD20的淋巴样恶性肿瘤患者中展现出良好的疗效和安全性[1],包括慢性和侵袭性B细胞非何杰金淋巴瘤。静脉注射的利妥昔单抗于1997年获得美国食品和药物管理局的批准,并于1998年获得欧洲药品管理局的批准,用于复发/难治性慢性非何杰金淋巴瘤的治疗。随后,它们分别在2009年和2010年获得慢性淋巴细胞白血病的使用批准[1]。
利妥昔单抗与CD20抗原具有高亲和力和特异性结合,CD20抗原广泛表达于恶性B细胞的绝大多数。利妥昔单抗对人类CD20的表观亲和常数,通过使用人类淋巴母细胞系的Scatchard分析确定,约为5.2 nmol/L [2]。对于活动性类风湿性关节炎的患者,利妥昔单抗也提供了显著的、临床上有意义的益处。在接受甲氨蝶呤治疗但仍患有活动性类风湿性关节炎的患者中,两次利妥昔单抗输注的单独或与环磷酰胺或继续甲氨蝶呤联合使用,分别在24周和48周时提供了显著的疾病症状改善[3]。
References:
[1]. Salles G, Barrett M, FoÀ R, et al. Rituximab in B-cell hematologic malignancies: a review of 20 years of clinical experience. Adv Ther. 2017;34(10):2232-2273.
[2]. Reff ME, Carner K, Chambers KS, et al. Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood. 1994;83:435-45.
[3]. Edwards JC, Szczepanski L, Szechinski J, et al. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med 2004;350:2572-2581
| Cas No. | 174722-31-7 | SDF | |
| 别名 | 利妥昔单抗; Anti-Human CD20 type I, Chimeric Antibody | ||
| Canonical SMILES | [Rituximab] | ||
| 分子式 | C6416H9874N1688O1987S44 | 分子量 | 144544.44 |
| 溶解度 | 储存条件 | Store at -80°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 | 0.0069 mL | 0.0346 mL | 0.0692 mL |
| 5 mM | 0.0014 mL | 0.0069 mL | 0.0138 mL |
| 10 mM | 0.0007 mL | 0.0035 mL | 0.0069 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。
Cellular and molecular signal transduction pathways modulated by Rituximab (rituxan, anti-CD20 mAb) in non-Hodgkin's lymphoma: implications in chemosensitization and therapeutic intervention
Oncogene 2005 Mar 24;24(13):2121-43.PMID:15789036DOI:10.1038/sj.onc.1208349
The clinical application of Rituximab (chimeric mouse anti-human CD20 mAb, Rituxan, IDEC-C2B8), alone and/or combined with chemotherapy, has significantly ameliorated the treatment outcome of patients with relapsed and refractory low-grade or follicular non-Hodgkin's lymphoma (NHL). The exact in vivo mechanisms of action of Rituximab are not fully understood, although antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and apoptosis have been suggested. We have proposed that modifications of the cellular signaling pathways by Rituximab may be crucial for its clinical response. The B-cell restricted cell surface phosphoprotein CD20 is involved in many cellular signaling events including proliferation, activation, differentiation, and apoptosis upon crosslinking. Monomeric Rituximab chemosensitizes drug-resistant NHL cells via selective downregulation of antiapoptotic factors through the type II mitochondrial apoptotic pathway. Several signaling pathways are affected by Rituximab which are implicated in the underlying molecular mechanisms of chemosensitization. ARL (acquired immunodeficiency syndrome (AIDS)-related lymphoma) and non-ARL cell lines have been examined as in vitro model systems. In ARL, Rituximab diminishes the activity of the p38MAPK signaling pathway resulting in inhibition of the interleukin (IL)-10/IL-10R autocrine/paracrine cytokine autoregulatory loop leading to the inhibition of constitutive STAT-3 activity and subsequent downregulation of Bcl-2 expression leading to chemosensitization. Rituximab upregulates Raf-1 kinase inhibitor protein (RKIP) expression in non-ARL cells. Through physical association with Raf-1 and nuclear factor kappaB (NF-kappa B)-inducing kinase (NIK), RKIP negatively regulates two major survival pathways, namely, the extracellular signal-regulated kinase1/2 (ERK1/2) and the NF-kappa B pathways, respectively. Downmodulation of the ERK1/2 and NF-kappa B pathways inhibits the transcriptional activity of AP-1 and NF-kappa B transcription factors, respectively, both of which lead to the downregulation of Bcl-(xL) (Bcl-2 related gene (long alternatively spliced variant of Bcl-x gene)) transcription and expression and sensitization to drug-induced apoptosis. Bcl-(xL)-overexpressing cells corroborated the pivotal role of Bcl-(xL) in chemosensitization. The specificity of rituximab-mediated signaling and functional effects were corroborated by the use of specific pharmacological inhibitors. Many patients do not respond and/or relapse and the mechanisms of unresponsiveness are unknown. Rituximab-resistant B-NHL clones were generated to investigate the acquired resistance to rituximab-mediated signaling, and chemosensitization. Resistant clones display different phenotypic, genetic and functional properties compared to wild-type cells. This review summarizes the data highlighting a novel role of Rituximab as a signal-inducing antibody and as a chemosensitizing agent through negative regulation of major survival pathways. Studies presented herein also reveal several intracellular targets modified by Rituximab, which can be exploited for therapeutic and prognostic purposes in the treatment of patients with rituximab- and drug-refractory NHL.