The class of DNA Ligase III inhibitors, in the context of indirect inhibition, includes a range of compounds that target various aspects of DNA synthesis, replication, and repair processes. These inhibitors do not act directly on DNA Ligase III but impact its activity by altering the cellular environment or the availability of substrates necessary for its function in DNA repair pathways. Agents such as Hydroxyurea, Methotrexate, and 5-Fluorouracil, which affect nucleotide biosynthesis, can indirectly impact DNA Ligase III by altering the availability of nucleotides required for DNA repair. Compounds like Cisplatin, Bleomycin, Doxorubicin, and Gemcitabine induce DNA damage, which could increase the demand on DNA repair pathways involving DNA Ligase III, potentially affecting its efficiency and capacity.
Furthermore, inhibitors targeting DNA replication enzymes, such as Etoposide, Camptothecin, and Aphidicolin, might influence DNA Ligase III by disrupting processes in which the enzyme is involved. The inhibition of topoisomerases and DNA polymerase affects DNA replication fidelity and integrity, potentially leading to an increased need for repair mechanisms in which DNA Ligase III participates. Olaparib, a PARP inhibitor, represents another mechanism of indirect influence on DNA Ligase III by modulating DNA repair pathways, particularly in response to single-strand breaks. N-Ethylmaleimide, which modifies cysteine residues, could indirectly influence the function of proteins involved in DNA repair, including DNA Ligase III.