title: Initial testing of JNJ-26854165 (Serdemetan) by the pediatric preclinical testing program.
abstract: JNJ-26854165 was originally developed as an activator of p53 capable of inducing apoptosis in cancer cell lines. In vitro, JNJ-26854165 demonstrated cytotoxic activity. The ALL cell line panel had a significantly lower median IC(50) (0.85 µM) than the remaining cell lines. In vivo JNJ-26854165 induced significant differences in EFS distribution compared to control in 18 of 37 solid tumors and in 5 of 7 of the evaluable ALL xenografts. Objective responses were observed in 4 of 37 solid tumor xenografts, and 2 of 7 ALL xenografts achieved PR or CR. Responses were noted in xenografts with both mutant and wild-type p53.
authors.affiliation: Cancer Therapy Evaluation Program, NCI, Bethesda, Maryland, USA. Malcolm.Smith@nih.gov
authors.forename: Malcolm A
authors.initials: MA
authors.lastname: Smith
authors.forename: Richard
authors.initials: R
authors.lastname: Gorlick
authors.forename: E Anders
authors.initials: EA
authors.lastname: Kolb
authors.forename: Richard
authors.initials: R
authors.lastname: Lock
authors.forename: Hernan
authors.initials: H
authors.lastname: Carol
authors.forename: John M
authors.initials: JM
authors.lastname: Maris
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Keir
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Morton
authors.forename: C Patrick
authors.initials: CP
authors.lastname: Reynolds
authors.forename: Min H
authors.initials: MH
authors.lastname: Kang
authors.forename: Janine
authors.initials: J
authors.lastname: Arts
authors.forename: Tarig
authors.initials: T
authors.lastname: Bashir
authors.forename: Michel
authors.initials: M
authors.lastname: Janicot
authors.forename: Raushan T
authors.initials: RT
authors.lastname: Kurmasheva
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Houghton
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002648:Child; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D012509:Sarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014363:Tryptamines / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D011838:Radiation-Sensitizing Agents; D014363:Tryptamines; D016159:Tumor Suppressor Protein p53; C568210:JNJ 26854165; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2