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Initial testing (stage 1) of LCL161, a SMAC mimetic, by the pediatric preclinical testing program
Author(s) -
Houghton Peter J.,
Kang Min H.,
Reynolds C. Patrick,
Morton Christopher L.,
Kolb E. Anders,
Gorlick Richard,
Keir Stephen T.,
Carol Hernan,
Lock Richard,
Maris John M.,
Billups Catherine A.,
Smith Malcolm A.
Publication year - 2012
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.23167
Subject(s) - medicine , in vivo , blood cancer , cancer , oncology , pharmacology , microbiology and biotechnology , biology
LCL161, a SMAC mimetic, was tested against the PPTP in vitro panel (1.0 nM to 10.0 µM) and the PPTP in vivo panels (30 or 75 mg/kg [solid tumors] or 100 mg/kg [ALL]) administered orally twice in a week. LCL161 showed a median relative IC 50 value of >10 µM, being more potent against several leukemia and lymphoma lines. In vivo LCL161 induced significant differences in EFS distribution in approximately one‐third of solid tumor xenografts (osteosarcoma and glioblastoma), but not in ALL xenografts. No objective tumor responses were observed. In vivo LCL161 demonstrated limited single agent activity against the pediatric preclinical models studied. Pediatr Blood Cancer 2012; 58: 636–639. © 2011 Wiley Periodicals, Inc.