2026-06-14T02:29:24Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/271602026-01-21T01:19:36Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19617

00925njm 22002777a 4500 dc Gargini, Ricardo author Segura-Collar, Berta author Garranzo-Asensio, Maria author Hortigüela, Rafael author Iglesias-Hernandez, Patricia author Lobato-Alonso, Daniel author Moreno-Raja, Miguel author Esteban-Martin, Santiago author Sepúlveda-Sánchez, Juan M author Nevola, Laura author Sánchez-Gómez, Pilar author 2022-01 Glioblastomas (GBMs) are the most frequent and highly aggressive brain tumors, being resistant to all cytotoxic and molecularly targeted agents tested so far. There is, therefore, an urgent need to find novel therapeutic approaches and/or alternative targets to bring treatment options to patients. Here, we first show that GBMs express high levels of N-MYC protein, a transcription factor involved in normal brain development. A novel stapled peptide designed to specifically target N-MYC protein monomer, IDP-410, is able to impair the formation of N-MYC/MAX complex and reduce the stability of N-MYC itself. As a result, the viability of GBM cells is compromised. Moreover, the efficacy is found dependent on the levels of expression of N-MYC. Finally, we demonstrate that IDP-410 reduces GBM growth in vivo when administered systemically, both in subcutaneous and intracranial xenografts, reducing the vascularization of the tumors, highlighting a potential relationship between the function of N-MYC and the expression of mesenchymal/angiogenic genes. Overall, our results strengthen the view of N-MYC as a therapeutic target in GBM and strongly suggest that IDP-410 could be further developed to become a first-in-class inhibitor of N-MYC protein, affecting not only tumor cell proliferation and survival, but also the interplay between GBM cells and their microenvironment. Gargini R, Segura-Collar B, Garranzo-Asensio M, Hortigüela R, Iglesias-Hernández P, Lobato-Alonso D, Moreno-Raja M, Esteban-Martin S, Sepúlveda-Sánchez JM, Nevola L, Sánchez-Gómez P. IDP-410: a Novel Therapeutic Peptide that Alters N-MYC Stability and Reduces Angiogenesis and Tumor Progression in Glioblastomas. Neurotherapeutics. 2022 Jan;19(1):408-420. doi: 10.1007/s13311-021-01176-6. Epub 2022 Jan 31. PMID: 35099769; PMCID: PMC9130446. 10.1007/s13311-021-01176-6 Neurotherapeutics 35099769 https://hdl.handle.net/20.500.12105/27160 Angiogenesis Glioblastoma Glioma N-MYC Peptide inhibitors Protein stability Tumor microenvironment IDP-410: a Novel Therapeutic Peptide that Alters N-MYC Stability and Reduces Angiogenesis and Tumor Progression in Glioblastomas.