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Synonyms: Bizengri® | MCLA-128 | PB4188 [3] | R040517 | zenocutuzumab-zbco
zenocutuzumab is an approved drug (FDA (2024))
Compound class:
Antibody
Comment: Zenocutuzumab (MCLA-128) is a humanized IgG1 bispecific anti-epidermal growth factor receptor 2/3 (HER2/HER3) monoclonal antibody [2-3]. It prevents binding of the ligand neuregulin 1 (NRG1) to HER3 and this suppresses HER2/HER3 dimerization, phosphorylation and downstream signalling [8]. Genetic NRG1 fusions have been identified as oncogenic drivers in a small number of tumour types [4,6]. Zenocutuzumab-mediated modulation inhibits signalling through the PI3K-AKT-mTOR pathway and reduces tumour cell growth and invasiveness. Low fucose glycoengineering enhances zenocutuzumab's antibody-dependent cellular cytotoxicity (ADCC) activity.
Ligand Activity Visualisation ChartsThese are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts. ✖ |
| References |
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1. Blair HA. (2025)
Zenocutuzumab: First Approval. Drugs, 85 (4): 591-597. [PMID:39994106] |
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2. de Vries Schultink AHM, Doornbos RP, Bakker ABH, Bol K, Throsby M, Geuijen C, Maussang D, Schellens JHM, Beijnen JH, Huitema ADR. (2018)
Translational PK-PD modeling analysis of MCLA-128, a HER2/HER3 bispecific monoclonal antibody, to predict clinical efficacious exposure and dose. Invest New Drugs, 36 (6): 1006-1015. [PMID:29728897] |
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3. Geuijen CAW, De Nardis C, Maussang D, Rovers E, Gallenne T, Hendriks LJA, Visser T, Nijhuis R, Logtenberg T, de Kruif J et al.. (2018)
Unbiased Combinatorial Screening Identifies a Bispecific IgG1 that Potently Inhibits HER3 Signaling via HER2-Guided Ligand Blockade. Cancer Cell, 33 (5): 922-936.e10. [PMID:29763625] |
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4. Gupta B, Borghaei L, Liu SV. (2025)
NRG1 Fusions: The New Kid on the Block. Curr Oncol Rep, 27 (2): 190-194. [PMID:39888568] |
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5. Kim DW, Schram AM, Hollebecque A, Nishino K, Macarulla T, Rha SY, Duruisseaux M, Liu SV, Al Hallak MN, Umemoto K et al.. (2024)
The phase I/II eNRGy trial: Zenocutuzumab in patients with cancers harboring NRG1 gene fusions. Future Oncol, 20 (16): 1057-1067. [PMID:38348690] |
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6. Liu SV. (2021)
NRG1 fusions: Biology to therapy. Lung Cancer, 158: 25-28. [PMID:34098222] |
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7. Schram AM, Goto K, Kim DW, Macarulla T, Hollebecque A, O'Reilly EM, Ou SI, Rodon J, Rha SY, Nishino K et al.. (2025)
Efficacy of Zenocutuzumab in NRG1 Fusion-Positive Cancer. N Engl J Med, 392 (6): 566-576. [PMID:39908431] |
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8. Schram AM, Odintsov I, Espinosa-Cotton M, Khodos I, Sisso WJ, Mattar MS, Lui AJW, Vojnic M, Shameem SH, Chauhan T et al.. (2022)
Zenocutuzumab, a HER2xHER3 Bispecific Antibody, Is Effective Therapy for Tumors Driven by NRG1 Gene Rearrangements. Cancer Discov, 12 (5): 1233-1247. [PMID:35135829] |
