Specific Topoisomerase I Inhibitors

Compounds that inhibit topoisomerase I can be divided into following two categories:80

a. Topoisomerase I suppressors, which are those compounds that inhibit the enzyme but do not stabilize the intermediate DNA-topoisomerase I covalent complex.

b. Topoisomerase I poisons, which act after DNA cleavage by inhibiting religa-tion. This can be achieved through three different mechanisms, involving (1) binding of the enzyme to the previously formed drug-DNA binary complex, (2) recognition of the enzyme-DNA binary complex by the drug, and (3) interaction of DNA with the drug-enzyme complex.81

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