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

Research output: Contribution to journal › Article › peer-review

21 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
Externally published	Yes

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.",

keywords = "Developmental therapeutics, MTOR inhibitor, Preclinical testing",

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

year = "2014",

month = aug,

doi = "10.1002/pbc.24989",

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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

Abstract

Keywords

ASJC Scopus subject areas

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