RMI2 Inhibitors

Chemical inhibitors of RMI2 can achieve functional inhibition through various mechanisms that interfere with the protein's role in DNA repair and homologous recombination. B02 and NSC 19630 target RAD51, a protein essential for the formation of the RMI2 complex, thereby disrupting its function. By inhibiting RAD51, these chemicals prevent the proper assembly of the RMI2 complex critical for effective DNA repair. Similarly, RI-1 covalently modifies RAD51, inhibiting its interaction with RMI2, and thus destabilizing the RMI2 functional complex. PIPER disrupts the RAD51 and BRCA2 interaction, indirectly impeding RMI2's function by preventing the necessary RAD51 filament formation. ML216 targets the Bloom syndrome protein (BLM), which forms a complex with RMI2, and by inhibiting BLM, it disrupts the BLM-RMI2 interaction essential for homologous recombination and DNA repair.

Further, Harpagoside inhibits the NF-κB pathway, which is involved in the regulation of DNA repair proteins including RMI2, leading to a decrease in RMI2's activity. Mirin inhibits the MRN complex, which is required for the recruitment of RMI2 to DNA double-strand break sites, thus inhibiting RMI2 by preventing its localization to sites of DNA damage. Etoposide indirectly inhibits RMI2 by inducing DNA damage that saturates the DNA repair pathways RMI2 is a part of. NU7026, a DNA-PK inhibitor, impedes DNA-PK's role in non-homologous end joining, a pathway where RMI2 also functions, thereby preventing RMI2 recruitment to DNA damage sites. PJ34 inhibits PARP, which is involved in single-strand break repair, thus indirectly disrupting the DNA repair processes and inhibiting RMI2 function. Finally, VE-821, an ATR inhibitor, can inhibit RMI2 function by impairing the ATR-mediated phosphorylation response to DNA damage, which is essential for the recruitment and action of proteins interacting with RMI2.