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[Cancer Research 60, 5937-5940, November 1, 2000]
© 2000 American Association for Cancer Research

Advances in Brief

Chloroquinoxaline Sulfonamide (NSC 339004) Is a Topoisomerase II{alpha}/ß Poison1

Hanlin Gao, Edith F. Yamasaki, Kenneth K. Chan, Linus L. Shen and Robert M. Snapka2

Departments of Radiology [H. G., E. F. Y., R. M. S.]; Molecular Virology, Immunology and Medical Genetics [H. G., R. M. S.]; College of Medicine [H. G., E. F. Y., R. M. S., K. K. C.]; and College of Pharmacy [K. K. C.], Ohio State University, Columbus, Ohio 43210, and Abbott Laboratories, Abbott Park, Illinois 60064 [L. L. S.]

Chloroquinoxaline sulfonamide (chlorosulfaquinoxaline, CQS, NSC 339004) is active against murine and human solid tumors. On the basis of its structural similarity to the topoisomerase IIß-specific drug XK469, CQS was tested and found to be both a topoisomerase-II{alpha} and a topoisomerase-IIß poison. Topoisomerase II poisoning by CQS is essentially undetectable in assays using the common protein denaturant SDS, but easily detectable with strong chaotropic protein denaturants. The finding that detection of topoisomerase poisoning can be so dependent on the protein denaturant used in the assay has implications for drug discovery efforts and for our understanding of topoisomerase poisons.




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Copyright © 2000 by the American Association for Cancer Research.