PMS2 Inhibitors

The chemical class of "PMS2 Inhibitors" encompasses a range of compounds that indirectly affect the functionality of PMS2, a key protein in the mismatch repair pathway of DNA. These inhibitors do not directly target PMS2 but exert their effects through the induction of DNA damages, alteration in DNA repair processes, or by modulating the cellular environment essential for the proper functioning of PMS2. The compounds in this class are characterized by their ability to induce various types of DNA damages, such as interstrand crosslinks, DNA strand breaks, and incorporation into DNA structures, which can overwhelm or obstruct the MMR system in which PMS2 operates. For instance, agents like Camptothecin, Etoposide, and Cisplatin work by inducing DNA lesions through inhibition of topoisomerases or formation of DNA crosslinks. These DNA damages create substrates that are challenging for the MMR system, leading to an inhibition of PMS2 function due to the overwhelming number of lesions or the creation of repair-resistant structures.

Other members of this class, such as Methotrexate and Hydroxyurea, impact DNA synthesis and repair indirectly. By altering nucleotide pool balance or inhibiting ribonucleotide reductase, these compounds can create an environment where DNA replication and repair are compromised, thereby inhibiting the function of PMS2 in the MMR system. Compounds like Azacitidine and Actinomycin D influence the functionality of PMS2 by altering DNA methylation patterns or disrupting DNA-dependent RNA synthesis, respectively. These alterations can affect the transcription of genes involved in DNA repair, including those related to the MMR pathway, thereby indirectly inhibiting PMS2. Furthermore, agents such as Doxorubicin, Mitomycin C, and Amsacrine act by intercalating into DNA or forming DNA cleavage complexes. These interactions lead to complex DNA damages that challenge the efficiency and capacity of the MMR system, including the functionality of PMS2.