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

doi:10.1002/pbc.24989

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

Pediatrics

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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 language	English (US)
Pages (from-to)	1486-1489
Number of pages	4
Journal	Pediatric Blood and Cancer
Volume	61
Issue number	8
DOIs	https://doi.org/10.1002/pbc.24989
State	Published - Aug 2014

Keywords

Developmental therapeutics
MTOR inhibitor
Preclinical testing

ASJC Scopus subject areas

Pediatrics, Perinatology, and Child Health
Hematology
Oncology

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Kang, M. H., Reynolds, C. P., Maris, J. M., Gorlick, R., Kolb, E. A., Lock, R., Carol, H., Keir, S. T., Wu, J., Lyalin, D., Kurmasheva, R. T., Houghton, P. J., & Smith, M. A. (2014). Initial testing (stage 1) of the investigational mTOR kinase inhibitor MLN0128 by the pediatric preclinical testing program. Pediatric Blood and Cancer, 61(8), 1486-1489. https://doi.org/10.1002/pbc.24989

Kang, MH, Reynolds, CP, Maris, JM, Gorlick, R, Kolb, EA, Lock, R, Carol, H, Keir, ST, Wu, J, Lyalin, D, Kurmasheva, RT, Houghton, PJ & Smith, MA 2014, 'Initial testing (stage 1) of the investigational mTOR kinase inhibitor MLN0128 by the pediatric preclinical testing program', Pediatric Blood and Cancer, vol. 61, no. 8, pp. 1486-1489. https://doi.org/10.1002/pbc.24989

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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.",

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year = "2014",

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AU - Kolb, E. Anders

AU - Lock, Richard

AU - Carol, Hernan

AU - Keir, Stephen T.

AU - Wu, Jianrong

AU - Lyalin, Dmitry

AU - Kurmasheva, Raushan T.

AU - Houghton, Peter J.

AU - Smith, Malcolm A.

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

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Keywords

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