FANCM Inhibitors

Chemical inhibitors classified as FANCM inhibitorsoperate by indirectly impeding the function of the FANCM protein. FANCM is integral to DNA repair, especially in the Fanconi anemia pathway, where it recognizes stalled replication forks and initiates repair processes. Chemicals that modulate the activity of enzymes and proteins upstream or downstream of FANCM can impact its functional state. Inhibition can occur through the disruption of key phosphorylation events required for FANCM's recruitment or activity, the prevention of protein-protein interactions necessary for its function, or the alteration of chromatin structures where FANCM operates. Agents such as ATR and ATM kinase inhibitors act by disrupting the phosphorylation of FANCM, which is a post-translational modification necessary for its activity in response to DNA damage. In contrast, compounds like Olaparib, which targets PARP enzymes, reduce the ability of FANCM to be recruited to sites of DNA damage where it plays a role in repair mechanisms. Further down the repair pathway, topoisomerase II inhibitors like Etoposide induce DNA lesions that necessitate FANCM involvement, thereby indirectly influencing its activity. Additionally, proteostasis regulators like HSP90 inhibitors can affect the stability and function of proteins that associate with FANCM, potentially impeding its role in the maintenance of genome integrity. These chemical inhibitors, through their interaction with various cellular pathways, ultimately impact the functional capacity of FANCM within the cell.