PMS1 Inhibitors

PMS1 Inhibitors encompasses a range of compounds that indirectly influence the activity of the Postmeiotic Segregation Increased 1 (PMS1) protein, a key component in the DNA mismatch repair (MMR) system. These inhibitors do not directly target the PMS1 protein but rather modulate the pathways and mechanisms in which PMS1 operates. This class includes several distinct groups of compounds, each characterized by its unique mode of action in affecting DNA repair processes. PARP inhibitors, such as Olaparib, Niraparib, Rucaparib, Talazoparib, and Veliparib, constitute a significant portion of this category. Their primary mechanism involves the inhibition of Poly (ADP-ribose) polymerase (PARP), a family of proteins that play a crucial role in repairing DNA single-strand breaks. The inhibition of PARP leads to the accumulation of single-strand DNA breaks, which, if left unrepaired, can result in more complex DNA damage. This escalation in DNA damage necessitates the involvement of more intricate repair mechanisms, including the MMR pathway where PMS1 is a critical player. By exacerbating the demand on the DNA repair machinery, these inhibitors indirectly challenge the functional capacity of PMS1.

PMS1 inhibitors includes topoisomerase inhibitors like Camptothecin, Irinotecan, Topotecan, and Etoposide. These compounds interfere with the action of topoisomerases, enzymes vital for DNA replication and transcription. By inhibiting these enzymes, the compounds induce DNA breaks and interfere with the replication process, leading to genomic instability. This instability, in turn, increases the burden on the DNA repair systems, including the MMR pathway. Alkylating agents such as Mitomycin C and platinum-based compounds like Cisplatin and Carboplatin also fall under this category. These agents induce cross-links in DNA, leading to replication errors and DNA damage. The response to this damage often requires the MMR system, thereby indirectly affecting the role of PMS1. The diversity of these compounds in their chemical structure and mode of action reflects the complexity of targeting a protein like PMS1, which does not lend itself to direct inhibition due to its integral role in the fundamental process of DNA repair.