title: Initial testing (stage 1) by the pediatric preclinical testing program of RO4929097, a γ-secretase inhibitor targeting notch signaling.
abstract: RO4929097 is a potent and selective inhibitor of γ-secretase and as a result is able to inhibit Notch pathway signaling. The activity of RO4929097 was evaluated against the in vivo panels of the Pediatric Preclinical Testing Program (PPTP). RO4929097 induced significant differences in event-free survival (EFS) distribution compared to control in 6 of 26 (23%) of the evaluable solid tumor xenografts and in 0 of 8 (0%) of the evaluable ALL xenografts. The most consistent tumor growth delay effects were noted in the osteosarcoma panel. RO4929097 at the dose and schedule evaluated demonstrated little antitumor activity against childhood cancer xenografts.
authors: A.I. duPont Hospital for Children, Wilmington, Delaware 19803, USA. eakolb@nemours.org
authors: E Anders
authors: EA
authors: Kolb
authors: Richard
authors: R
authors: Gorlick
authors: Stephen T
authors: ST
authors: Keir
authors: John M
authors: JM
authors: Maris
authors: Richard
authors: R
authors: Lock
authors: Hernan
authors: H
authors: Carol
authors: Raushan T
authors: RT
authors: Kurmasheva
authors: C Patrick
authors: CP
authors: Reynolds
authors: Min H
authors: MH
authors: Kang
authors: Jianrong
authors: J
authors: Wu
authors: Peter J
authors: PJ
authors: Houghton
authors: Malcolm A
authors: MA
authors: Smith
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D051880:Receptors, Notch / Q000037:antagonists & inhibitors* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D023041:Xenograft Model Antitumor Assays; D005466:Fluorocarbons
chemical_list: D053829:Amyloid Precursor Protein Secretases; D001552:Benzazepines; D051880:Receptors, Notch; C545185:2,2-dimethyl-N-(6-oxo-6,7-dihydro-5H-dibenzo(b,d)azepin-7-yl)-N'-(2,2,3,3,3-pentafluoropropyl)malonamide; D005466:Fluorocarbons