Abstract
This is a preclinical study of BO-0742, a derivative of 3-(9-acridinylamino)-5-hydroxymethyl-aniline (AHMA) and N-mustard, as an anti-cancer agent. MTS assays revealed a broad spectrum of anti-cancer activities in vitro, with the greatest cytotoxicity against leukemia and neuroblastoma including those with drug resistant characteristics, and a good therapeutic index with leukemia being 10-40 times more sensitive to BO-0742 than hematopoietic progenitors. Administration of BO-0742 at an optimal dose schedule based on its pharmacokinetics significantly suppressed the growth of xenografts of human breast and ovarian cancers in mice. Thus, BO-0742 is a potent anti-cancer agent worthy of further clinical development.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / physiology
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Acridines / pharmacokinetics
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Acridines / pharmacology*
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Aniline Compounds / pharmacokinetics
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Aniline Compounds / pharmacology*
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Animals
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Antineoplastic Agents / pharmacokinetics
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Antineoplastic Agents / pharmacology*
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Cell Line, Tumor
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Drug Resistance, Neoplasm
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Hematopoietic Stem Cells / drug effects
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Humans
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Leukemia / drug therapy*
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Leukemia / pathology
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Male
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Mice
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Multidrug Resistance-Associated Proteins / physiology
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Neoplasms / drug therapy*
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Neoplasms / pathology
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Nitrogen Mustard Compounds / pharmacology*
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Xenograft Model Antitumor Assays
Substances
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3-(9-acridinylamino)-5-hydroxymethylaniline
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ABCB1 protein, human
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ATP Binding Cassette Transporter, Subfamily B
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Acridines
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Aniline Compounds
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Antineoplastic Agents
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BO-0742
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Multidrug Resistance-Associated Proteins
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Nitrogen Mustard Compounds
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multidrug resistance-associated protein 1