Topo IIIβ Inhibitors

The chemical class of Topo IIIβ Inhibitors encompasses a range of compounds that primarily target the topoisomerase family of enzymes, which are essential for resolving topological problems in DNA during replication and transcription. These compounds can indirectly affect Topo IIIβ by altering the dynamic equilibrium of DNA topology, influencing the availability and structure of DNA substrates that Topo IIIβ acts upon, and modulating the cellular response to DNA damage.

Compounds such as camptothecin, topotecan, and β-lapachone target topoisomerase I, creating stabilized complexes between the enzyme and DNA, leading to breaks in the DNA strands. While these compounds exhibit specificity towards Topo I, the resulting DNA damage and the cellular responses to such damage can have a cascading effect on the functions of other topoisomerases, including Topo IIIβ. The altered landscape of DNA damage and repair may create conditions where Topo IIIβ's activity is indirectly influenced. On the other hand, compounds like etoposide, teniposide, amsacrine, ICRF-193, novobiocin, mitoxantrone, merbarone, dexrazoxane, and fostriecin target topoisomerase II. This enzyme is closely related to Topo IIIβ in terms of its role in managing DNA supercoiling and tangles during DNA replication. The inhibition of topoisomerase II can lead to an increased demand on other enzymes involved in these processes, including Topo IIIβ. By stabilizing the DNA-enzyme complexes, intercalating into DNA, or altering the enzyme conformation, these compounds can cause an accumulation of topological stress on DNA. Such stress may indirectly require compensatory activity by Topo IIIβ, making it a downstream target affected by these inhibitors.