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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. Copyright © 2011 Wiley Periodicals, Inc.


Peter J Houghton, Min H Kang, C Patrick Reynolds, Christopher L Morton, E Anders Kolb, Richard Gorlick, Stephen T Keir, Hernan Carol, Richard Lock, John M Maris, Catherine A Billups, Malcolm A Smith. Initial testing (stage 1) of LCL161, a SMAC mimetic, by the Pediatric Preclinical Testing Program. Pediatric blood & cancer. 2012 Apr;58(4):636-9

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PMID: 21681929

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