Trastuzumab (Anti-Human HER2, Humanized Antibody)
(Synonyms: 曲妥珠单抗; Anti-Human HER2, Humanized Antibody) 目录号 : GC34215
曲妥珠单抗是一种针对 HER2 的完全人源化单克隆抗体，它结合受体的外部结构域，并通过抗体依赖性细胞毒性、减少细胞外结构域脱落、抑制二聚化和可能的受体下调来发挥作用。
Cas No.:180288-69-1
Sample solution is provided at 25 µL, 10mM.
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Trastuzumab is a fully humanized monoclonal antibody directed at HER2 which binds the external domain of the receptor and exerts its action via a combination of antibody-dependent cytotoxicity, reduced shedding of the extracellular domain, inhibition of dimerization and possibly receptor downregulation[1,2]. Trastuzumab is used as a standard treatment for breast and metastatic gastric cancer when the cancer cells overexpress HER2[3].
Trastuzumab combined with MZ1 significantly decreased cell proliferation, the formation of three-dimensional structures and cellular invasion compared to either of the drugs alone[4]. Trastuzumab treated HER2-overexpressing breast cancer cell lines results in induction of p27KIP1 and the Rb-related protein, p130, which in turn significantly reduces the number of cells undergoing S-phase. A number of other phenotypic changes are observed in vitro as a consequence of trastuzumab binding to HER2-overexpressing cells[5]. Trastuzumab-dendrimer-fluorine drug delivery system is a new form of trastuzumab to treat breast cancer cells in vitro. The potential of Trastuzumab-dendrimer-fluorine drug delivery system is more efficient than trastuzumab alone[6]
Trastuzumab causes a significant growth inhibition of the outgrowth of macroscopic JIMT-1 xenograft tumors in both nude and SCID mice[7]. The administration of MZ1 and trastuzumab induced a reduction in tumor progression, while individual treatments failed to do so[4]
References:
[1]. Ning G, Zhu Q, et al. A novel treatment strategy for lapatinib resistance in a subset of HER2-amplified gastric cancer. BMC Cancer. 2021;21(1):923. Published 2021 Aug 16. doi:10.1186/s12885-021-08283-9
[2]. Okines AF, Cunningham D. Trastuzumab: a novel standard option for patients with HER-2-positive advanced gastric or gastro-oesophageal junction cancer. Therap Adv Gastroenterol. 2012 Sep;5(5):301-18.
[3]. Sarosiek T, Morawski P. Trastuzumab and its biosimilars [Trastuzumab and its biosimilars]. Pol Merkur Lekarski. 2018 May 25;44(263):253-257. Polish.
[4]. Noblejas-López MDM, Nieto-Jiménez C, et al. MZ1 co-operates with trastuzumab in HER2 positive breast cancer. J Exp Clin Cancer Res. 2021 Mar 19;40(1):106.
[5]. Sliwkowski MX, Lofgren JA, et al. Nonclinical studies addressing the mechanism of action of trastuzumab (Herceptin). Semin Oncol. 1999 Aug;26(4 Suppl 12):60-70.
[6]. Bartusik-Aebisher D, Chrzanowski G, et al. An analytical study of Trastuzumab-dendrimer-fluorine drug delivery system in breast cancer therapy in vitro. Biomed Pharmacother. 2021 Jan;133:111053.
[7]. Barok M, Isola J, et al. Trastuzumab causes antibody-dependent cellular cytotoxicity-mediated growth inhibition of submacroscopic JIMT-1 breast cancer xenografts despite intrinsic drug resistance. Mol Cancer Ther. 2007 Jul;6(7):2065-72.
曲妥珠单抗是一种针对 HER2 的完全人源化单克隆抗体，它结合受体的外部结构域，并通过抗体依赖性细胞毒性、减少细胞外结构域脱落、抑制二聚化和可能的受体下调来发挥作用[1,2]。当癌细胞过度表达 HER2[3] 时，曲妥珠单抗被用作乳腺癌和转移性胃癌的标准治疗方法。
与单独使用任何一种药物相比，曲妥珠单抗联合 MZ1 可显着降低细胞增殖、三维结构的形成和细胞侵袭[4]。曲妥珠单抗处理的 HER2 过表达乳腺癌细胞系导致 p27KIP1 和 Rb 相关蛋白 p130 的诱导，这反过来显着减少了经历 S 期的细胞数量。由于曲妥珠单抗与 HER2 过表达细胞结合，在体外观察到许多其他表型变化[5]。曲妥珠单抗-树枝状大分子-氟药物递送系统是一种新形式的曲妥珠单抗，可在体外治疗乳腺癌细胞。曲妥珠单抗-树枝状大分子-氟药物递送系统的潜力比单独使用曲妥珠单抗更有效[6]
曲妥珠单抗可显着抑制裸鼠和 SCID 小鼠肉眼可见的 JIMT-1 异种移植肿瘤的生长[7]。 MZ1 和曲妥珠单抗的给药诱导了肿瘤进展的减缓，而单独的治疗则未能做到这一点[4]
| Cell experiment [1]: | |
|
Cell lines |
Breast cancer HER2+ cells BT474 and SKBR3 |
|
Preparation Method |
Cells were seeded on 48-wells plates and were treated 24h later with indicated doses of each drug (MZ1 and trastuzumab), alone or in combination. Cell medium was replaced at 72h with MTT solution for 45min at 37℃. |
|
Reaction Conditions |
25-100nM MZ1, 10nM trastuzumab, 25-100nM MZ1+trastuzumab |
|
Applications |
MZ1 showed the highest antiproliferative effect. Trastuzumab combined with MZ1 induced a more profound antiproliferative effect than the administration of single agents in both BT474 and SKBR3 cells. A synergistic interaction between trastuzumab and MZ1 in BT474 cells and an additive interaction in SKBR3 cells was observed. |
| Animal experiment [2]: | |
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Animal models |
Female BALB/c nude mice, 4-6 weeks |
|
Preparation Method |
Xenografts were used for the experiments once the tumor volume reached about 150-200mm3. Mice were randomly assigned to different groups as follows: (i) vehicle; (ii) trastuzumab 10mg/kg twice weekly of intraperitoneal injection; (iii) AZD5438 20mg/kg daily by oral gavage; (iv) AZD5438+trastuzumab, for 3 weeks. Experiments were ended once the tumor volume surpassed 1500mm3 or mouse weight loss reached 20%. |
|
Dosage form |
10mg/kg trastuzumab, 20mg/kg AZD5438 |
|
Applications |
Trastuzumab exerted antitumor effects in ERBB2-positive AFPGC PDX models. Statistically significant differences were also present in the tumor volume between the group treated with AZD5438 combined with trastuzumab and those treated with AZD5438 or trastuzumab alone in ERBB2 and CCNE1 co-amplified PDX models, but the results were not observed in CCNE1 non-amplified PDX models. |
|
References: [1]. Noblejas-López MDM, Nieto-Jiménez C, et al. MZ1 co-operates with trastuzumab in HER2 positive breast cancer. J Exp Clin Cancer Res. 2021 Mar 19;40(1):106. [2]. Lu J, Ding Y, et al. Whole-exome sequencing of alpha-fetoprotein producing gastric carcinoma reveals genomic profile and therapeutic targets. Nat Commun. 2021;12(1):3946. Published 2021 Jun 24. doi:10.1038/s41467-021-24170-0 |
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| Cas No. | 180288-69-1 | SDF | |
| 别名 | 曲妥珠单抗; Anti-Human HER2, Humanized Antibody | ||
| Canonical SMILES | [Trastuzumab] | ||
| 分子式 | C6470H10012N1726O2013S42 | 分子量 | 145145.09 |
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 0.0069 mL | 0.0344 mL | 0.0689 mL |
| 5 mM | 0.0014 mL | 0.0069 mL | 0.0138 mL |
| 10 mM | 0.0007 mL | 0.0034 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，
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2.
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Purity: >99.50%
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