Initial testing (stage 1) of the investigational mTOR kinase inhibitor MLN0128 by the pediatric preclinical testing program. Issue 8 (20th February 2014)

• Record Type: Journal Article
• Authors: 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.
• Is Part Of: Pediatric blood & cancer. Volume 61:Issue 8(2014:Aug.)
• Page Start: 1486
• Page End: 1489
• Publication Date: 2014-02-20
• Subjects: Tumors in children -- Periodicals; Blood -- Diseases -- Periodicals; Cancer in children -- Periodicals; 618.92
• DOI: 10.1002/pbc.24989
• Languages: English
• ISSNs: 1545-5009

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <sec id="pbc24989-sec-0001" sec-type="section"> <p>MLN0128 is an investigational small molecule ATP‐competitive inhibitor of the serine/threonine kinase mTOR. MLN0128 was tested against the <italic>in vitro</italic> panel at concentrations ranging from 0.1 nM to 1 μM and against the PPTP <italic>in vivo</italic> panels at a dose of 1 mg/kg administered orally daily × 28. <italic>In vitro</italic> the median relative IC₅₀ concentration was 19 nM. <italic>In vivo</italic> 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.</p> </sec> </abstract>