Journal
PEDIATRIC BLOOD & CANCER
Volume 58, Issue 4, Pages 636-639Publisher
WILEY PERIODICALS, INC
DOI: 10.1002/pbc.23167
Keywords
developmental therapeutics; preclinical testing; SMAC mimetic
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Funding
- National Cancer Institute [NO1-CM-42216, CA21765, CA108786]
- Novartis Pharmaceuticals [LCL161]
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LCL161, a SMAC mimetic, was tested against the PPTP in vitro panel (1.0?nM to 10.0?mu M) 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 IC50 value of >10?mu M, 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: 636639. (c) 2011 Wiley Periodicals, Inc.
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