title: BO-0742, a derivative of AHMA and N-mustard, has selective toxicity to drug sensitive and drug resistant leukemia cells and solid tumors.
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.
authors.affiliation: Cellular and Molecular Medicine, Genomics Research Center, 128 Academia Sinica, Section 2, Taipei, Taiwan.
authors.forename: Chien-Hsin
authors.initials: CH
authors.lastname: Lee
authors.forename: Ting-Chao
authors.initials: TC
authors.lastname: Chou
authors.forename: Tsann-Long
authors.initials: TL
authors.lastname: Su
authors.forename: John
authors.initials: J
authors.lastname: Yu
authors.forename: Li-En
authors.initials: LE
authors.lastname: Shao
authors.forename: Alice L
authors.initials: AL
authors.lastname: Yu
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology; D000166:Acridines / Q000493:pharmacokinetics / Q000494:pharmacology*; D000814:Aniline Compounds / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009588:Nitrogen Mustard Compounds / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000166:Acridines; D000814:Aniline Compounds; D000970:Antineoplastic Agents; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009588:Nitrogen Mustard Compounds; C466640:3-(9-acridinylamino)-5-hydroxymethylaniline; C513055:ABCB1 protein, human; C539194:BO-0742; C421109:multidrug resistance-associated protein 1