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.
Copyright © 2011 Wiley Periodicals, Inc.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Brain Neoplasms / drug therapy*
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Brain Neoplasms / metabolism
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Brain Neoplasms / pathology
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Child
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Drug Evaluation, Preclinical
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Female
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Humans
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Mice
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Mice, Inbred BALB C
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Mice, Inbred NOD
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Mice, SCID
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Neuroblastoma / drug therapy*
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Neuroblastoma / metabolism
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Neuroblastoma / pathology
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
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Proto-Oncogene Proteins c-mdm2 / genetics
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Proto-Oncogene Proteins c-mdm2 / metabolism
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Radiation-Sensitizing Agents / pharmacology*
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Sarcoma / drug therapy*
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Sarcoma / metabolism
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Sarcoma / pathology
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Tryptamines / pharmacology*
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Tumor Cells, Cultured
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Protein p53 / metabolism
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Xenograft Model Antitumor Assays
Substances
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Radiation-Sensitizing Agents
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Tryptamines
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Tumor Suppressor Protein p53
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JNJ 26854165
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MDM2 protein, human
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Proto-Oncogene Proteins c-mdm2