Zenocutuzumab
(Synonyms: MCLA-128; PB4188; R040517) 目录号 : GC70169Zenocutuzumab是一种双特异性人源化 IgG1 抗体，包含两个不同的Fab臂，靶向HER2和HER3的细胞外结构域。
Cas No.:1969309-56-5
Sample solution is provided at 25 µL, 10mM.
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Zenocutuzumab is a bispecific humanized IgG1 antibody containing two different Fab arms that target the extracellular domains of HER2 and HER3[1]. Zenocutuzumab specifically binds to the HER3 receptor, blocks its interaction with the ligand, and inhibits downstream PI3K/AKT and MAPK/ERK signaling pathway activation[2, 3]. Zenocutuzumab can be used to treat NRG1 fusion-positive cancers, which are oncogenic drivers of pancreatic cancer and other solid tumors[4].
In vitro, treatment of homologous human bronchial epithelial cell lines (HBEC) expressing CD74-NRG1 or VAMP2-NRG1 fusions with Zenocutuzumab (0.001-1000nM) for 96h significantly inhibited cell growth. HBEC cells with NRG1 fusions were approximately 40,000-fold more sensitive to Zenocutuzumab than parental control cells[5]. Zenocutuzumab (0.1-1000nM) treatment of HBEC-CD74NRG1, LUAD-0061AS3 and MDA-MB-175-VII cells dose-dependently reduced the phosphorylation of HER3, HER2 and HER4[5].
In vivo, Zenocutuzumab (2.5-25mg/kg) treated with patient-derived xenograft (PDX) model mice by intraperitoneal injection inhibited tumor growth in a dose-dependent manner and caused tumor regression[5].
References:
[1] Antonarelli G, Giugliano F, Corti C, et al. Research and clinical landscape of bispecific antibodies for the treatment of solid malignancies[J]. Pharmaceuticals, 2021, 14(9): 884.
[2] Yin L. Gene Editing in ErbB/HER Family-Mediated Cancer Immunology[J]. 2025.
[3] Bhagyalalitha M, Shankaranarayana A H, Kumar S A, et al. Advances in HER2-Targeted Therapies: From monoclonal antibodies to dual inhibitors developments in cancer treatment[J]. Bioorganic Chemistry, 2024: 107695.
[4] Schram A M, O'Reilly E M, O'Kane G M, et al. Efficacy and safety of zenocutuzumab in advanced pancreas cancer and other solid tumors harboring NRG1 fusions[J]. 2021.
[5] Schram A M, Odintsov I, Espinosa-Cotton M, et al. Zenocutuzumab, a HER2xHER3 bispecific antibody, is effective therapy for tumors driven by NRG1 gene rearrangements[J]. Cancer Discovery, 2022, 12(5): 1233-1247.
Zenocutuzumab是一种双特异性人源化 IgG1 抗体，包含两个不同的Fab臂，靶向HER2和HER3的细胞外结构域[1]。Zenocutuzumab通过特异性结合HER3受体，阻断其与配体的相互作用，抑制下游PI3K/AKT和MAPK/ERK信号通路激活[2, 3]。Zenocutuzumab能够用于治疗NRG1融合阳性癌症，NRG1融合蛋白是胰腺癌和其他实体肿瘤的致癌驱动因素[4]。
在体外，Zenocutuzumab（0.001-1000nM）处理表达CD74-NRG1或 VAMP2-NRG1融合的同源人支气管上皮细胞系（HBEC）96h，显著抑制了细胞的生长，具有NRG1融合的HBEC细胞对Zenocutuzumab的敏感性比亲本对照细胞高出约40000倍[5]。Zenocutuzumab（0.1-1000nM）处理HBEC-CD74NRG1、LUAD-0061AS3和MDA-MB-175-VII细胞，剂量依赖性地降低了HER3、HER2和HER4的磷酸化[5]。
在体内，Zenocutuzumab（2.5-25mg/kg）通过腹腔注射治疗患者来源异种移植（PDX）模型小鼠，以剂量依赖性方式抑制了肿瘤生长，引起了肿瘤消退[5]。
| Cell experiment [1]: | |
Cell lines | Isogenic human bronchiolar epithelial cell lines (HBEC) expressing either a CD74-NRG1 or a VAMP2-NRG1 fusion |
Preparation Method | Cells were treated with 0.001-1000nM Zenocutuzumab for 96h, and then growth was determined using AlamarBlue viability dye. Valuesare expressed relative to the vehicle-treated control (100%). Data were analyzed by nonlinear regression to determine IC50 for inhibition of growth. |
Reaction Conditions | 0.001-1000nM; 96h |
Applications | Growth of isogenic human bronchiolar epithelial cell lines (HBEC) expressing either a CD74-NRG1 or a VAMP2-NRG1 fusion was reduced by subnanomolar concentrations of Zenocutuzumab. In contrast, growth of the isogenic control HBEC line remained largely unaffected by Zenocutuzumab treatment. HBEC cells with NRG1 fusions were approximately 40,000 times more sensitive to Zenocutuzumab than the parental control cells. |
| Animal experiment [1]: | |
Animal models | NSG (LUAD-0061AS3)、BALB/c nude (OV-10-0050)、 athymic nude (ST2891, ST3204, and CTG-0953) mice |
Preparation Method | Crushed patient-derived xenograft (PDX) tumor samples were mixed with matrigel (50%) and injected into the subcutaneous flank of 6- to 12-week-old female NSG (LUAD-0061AS3), BALB/c nude (OV-10-0050), or athymic nude (ST2891, ST3204, and CTG-0953) mice. When tumors reached Approximately 125 to 250mm3, mice were randomized into groups of 5 to 10 and treatment commenced. Animals bearing established PDX tumors were treated once per week with Zenocutuzumab (2.5, 8, or 25mg/kg). Zenocutuzumab was administered in phosphate-buffered saline by injection into the peritoneal cavity once per week. Mice were observed daily throughout the treatment period for signs of morbidity and mortality. Tumor length and width as well as animal weights were measured twice weekly. |
Dosage form | 2.5, 8, 25mg/kg; once per week; i.p. |
Applications | Each of the three Zenocutuzumab doses caused a significant reduction in tumor volume. |
References: | |
| Cas No. | 1969309-56-5 | SDF | Download SDF |
| 别名 | MCLA-128; PB4188; R040517 | ||
| 分子式 | 分子量 | 145.76 kDa | |
| 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 | 6.8606 mL | 34.303 mL | 68.6059 mL |
| 5 mM | 1.3721 mL | 6.8606 mL | 13.7212 mL |
| 10 mM | 0.6861 mL | 3.4303 mL | 6.8606 mL |
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| 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 | ||||||||||
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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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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。
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