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Initial testing (stage 1) of the investigational mTOR kinase inhibitor MLN0128 by the pediatric preclinical testing program
Author(s) -
Kang Min H.,
Reynolds C. Patrick,
Maris John M.,
Gorlick Richard,
Kolb E. Anders,
Lock Richard,
Carol Hernan,
Keir Stephen T.,
Wu Jianrong,
Lyalin Dmitry,
Kurmasheva Raushan T.,
Houghton Peter J.,
Smith Malcolm A.
Publication year - 2014
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.24989
Subject(s) - in vivo , preclinical testing , medicine , pharmacology , kinase , in vitro , chemistry , biology , biochemistry , medical physics , genetics
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 0.1 nM to 1 μM and against the PPTP in vivo panels at a dose of 1 mg/kg administered orally daily × 28. In vitro the median relative IC 50 concentration was 19 nM. 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. Pediatr Blood Cancer 2014; 61:1486–1489. © 2014 Wiley Periodicals, Inc.