BO-0742, a derivative of AHMA and N-mustard, has selective toxicity to drug sensitive and drug resistant leukemia cells and solid tumors.
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.
Lee
Chien-Hsin
CH
Cellular and Molecular Medicine, Genomics Research Center, 128 Academia Sinica, Section 2, Taipei, Taiwan.
Chou
Ting-Chao
TC
Su
Tsann-Long
TL
Yu
John
J
Shao
Li-En
LE
Yu
Alice L
AL
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
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