Zenocutuzumab (Synonyms: MCLA-128; PB4188; R040517) |
| Catalog No.GC70169 |
Zenocutuzumab (MCLA-128) is a dual-specificity humanized IgG1 antibody that contains two different Fab arms targeting the extracellular domains of HER2 and HER3.
Products are for research use only. Not for human use. We do not sell to patients.
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.
| 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 | |
| Sinónimos | MCLA-128; PB4188; R040517 | ||
| Formula | M.Wt | 145.76 kDa | |
| Solubility | Storage | Store at -80°C | |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
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