Evaluation of VTP-50469, a menin-MLL1 inhibitor, against Ewing sarcoma xenograft models by the pediatric preclinical testing consortium

Raushan T. Kurmasheva, Abhik Bandyopadhyay, Edward Favours, Vanessa Del Pozo, Samson Ghilu, Doris A. Phelps, Gerard M. McGeehan, Stephen W. Erickson, Malcolm A. Smith, Peter J. Houghton

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article numbere28284
JournalPediatric Blood and Cancer
Volume67
Issue number7
DOIs
StatePublished - Jul 1 2020

Keywords

  • Ewing sarcoma
  • pediatric oncology
  • xenograft

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

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