title: Initial testing (stage 1) of LCL161, a SMAC mimetic, by the Pediatric Preclinical Testing Program.
abstract: 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.
authors.affiliation: Nationwide Children's Hospital, Columbus, Ohio 43205, USA. peter.houghton@nationwidechildrens.org
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Houghton
authors.forename: Min H
authors.initials: MH
authors.lastname: Kang
authors.forename: C Patrick
authors.initials: CP
authors.lastname: Reynolds
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Morton
authors.forename: E Anders
authors.initials: EA
authors.lastname: Kolb
authors.forename: Richard
authors.initials: R
authors.lastname: Gorlick
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Keir
authors.forename: Hernan
authors.initials: H
authors.lastname: Carol
authors.forename: Richard
authors.initials: R
authors.lastname: Lock
authors.forename: John M
authors.initials: JM
authors.lastname: Maris
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Billups
authors.forename: Malcolm A
authors.initials: MA
authors.lastname: Smith
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy*; D009842:Oligopeptides / Q000494:pharmacology*; D057786:Peptidomimetics / Q000494:pharmacology*; D014183:Transplantation, Heterologous; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D009842:Oligopeptides; D057786:Peptidomimetics; C532637:SMAC peptide