Evaluation of VTP-50469, a Menin-MLL1 Inhibitor, Against Ewing Sarcoma Xenograft Models by the Pediatric Preclinical Testing Consortium
| Autor: | Abhik M Bandyopadhyay, Samson Ghilu, Edward Favours, Vanessa Del Pozo, Raushan T. Kurmasheva, Stephen W. Erickson, Malcolm A. Smith, Gerard McGeehan, Peter J. Houghton, Doris A. Phelps |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Drug Evaluation
Preclinical Antineoplastic Agents Bone Neoplasms Sarcoma Ewing Pediatrics Leukemia cell line Article 03 medical and health sciences Mice 0302 clinical medicine Cell Line Tumor Proto-Oncogene Proteins medicine Animals Humans IC50 business.industry Hematology Histone-Lysine N-Methyltransferase medicine.disease Xenograft Model Antitumor Assays In vitro Leukemia Oncology Tumor progression Preclinical testing Cell culture 030220 oncology & carcinogenesis Pediatrics Perinatology and Child Health Cancer research Female Sarcoma business Myeloid-Lymphoid Leukemia Protein 030215 immunology |
| Zdroj: | Pediatr Blood Cancer |
| Popis: | Background VTP-50469 is a potent inhibitor of the menin-MLL1 interaction and is implicated in signaling downstream of EWSR1-FLI1. Procedure VTP-50469 was evaluated against seven Ewing sarcoma (EwS) xenograft models and in vitro against EwS cell lines. Results VTP-50469 showed limited antitumor activity, statistically significantly slowing tumor progression in four tumor models but with no evidence of tumor regression. In vitro, the IC50 concentration was 10 nM for the mixed lineage leukemia (MLL)-rearranged leukemia cell line MV4;11, but > 3 μM for EwS cell lines. Conclusions In contrast to its high level of activity against MLL1-rearranged leukemia xenografts, VTP-50469 shows little activity against EwS models. |
| Databáze: | OpenAIRE |
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