hPMS1 Inhibitors

Chemical inhibitors of hPMS1 include a variety of compounds that interfere with the protein's role in DNA repair and damage response pathways. Mirin, by targeting the Mre11-Rad50-Nbs1 (MRN) complex, disrupts the initial recognition of DNA double-strand breaks, a crucial step for hPMS1 to exert its repair function. Similarly, NU7026, as a DNA-PK inhibitor, prevents the phosphorylation cascade essential for the activation of hPMS1, thereby inhibiting its role in the repair process. KU-55933, an ATM kinase inhibitor, and VE-821, an ATR inhibitor, both impede upstream signaling required for hPMS1's recruitment and function at DNA damage sites. LY294002 and Wortmannin, both PI3K inhibitors, curb the phosphorylation events upstream of hPMS1's activation, which is necessary for its role in DNA repair mechanisms.

Moreover, CX-5461, by impeding RNA Polymerase I, indirectly affects the transcription of key players in the DNA repair pathway that collaborate with hPMS1. The action of BMH-21, which induces nucleolar stress, can lead to the destabilization of the cellular environment and protein interactions necessary for hPMS1 to function effectively in DNA repair. Olaparib and PJ-34, both PARP inhibitors, alter the PARylation landscape of the cell, which can reduce the recruitment and functionality of hPMS1 at sites of DNA damage. Etoposide, through its stabilization of topoisomerase II-DNA complexes, creates an obstruction that can hamper processes where hPMS1 is involved in the resolution of DNA strand breaks. Lastly, SN-38, the active metabolite of irinotecan, inhibits Topoisomerase I, leading to DNA damage accumulation and potentially disrupting hPMS1's ability to mediate the DNA repair response. Each of these chemicals targets specific molecular interactions and pathways that are crucial for the proper functioning of hPMS1, thereby achieving inhibition of the protein's activity in the cellular context.