Initial testing (stage 1) of the investigational mTOR kinase inhibitor MLN0128 by the pediatric preclinical testing program

Min H. Kang, C. Patrick Reynolds, John M. Maris, Richard Gorlick, E. Anders Kolb, Richard Lock, Hernan Carol, Stephen T. Keir, Jianrong Wu, Dmitry Lyalin, Raushan T. Kurmasheva, Peter J. Houghton, Malcolm A. Smith

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

MLN0128 is an investigational small molecule ATP-competitive inhibitor of the serine/threonine kinase mTOR. MLN0128 was tested against the in vitro panel at concentrations ranging from 0.1nM to 1μM and against the PPTP in vivo panels at a dose of 1mg/kg administered orally daily×28. In vitro the median relative IC50 concentration was 19nM. In vivo MLN0128 induced significant differences in EFS in 24/31 (77%) solid tumor models, but 0/7 ALL xenografts. The modest activity observed for MLN0128 against the PPTP preclinical models is similar to that previously reported for another TOR kinase inhibitor.

Original languageEnglish
Pages (from-to)1486-1489
Number of pages4
JournalPediatric Blood and Cancer
Volume61
Issue number8
DOIs
StatePublished - Aug 2014

Funding

FundersFunder number
National Childhood Cancer Registry – National Cancer InstituteP30CA021765

    Keywords

    • Developmental therapeutics
    • MTOR inhibitor
    • Preclinical testing

    ASJC Scopus subject areas

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

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