PIP-199 is a selective inhibitor of RMI (RecQ-mediated genome instability protein) core complex/MM2 interaction, with an IC50 of 36 μM. MM2 is the binding site of RMI complex on Fanconi anemia complementation group M protein (FANCM). PIP-199 can be used for the research of sensitizing resistant tumors to DNA crosslinking chemotherapeutics[1].
Induction of the Fanconi anemia (FA) DNA repair pathway is a common mechanism by which tumors evolve resistance to DNA crosslinking chemotherapies[1].Proper execution of the FA pathway requires interaction between the FANCM and the RMI complex, and mutations that disrupt FANCM/RMI interactions sensitize cells to DNA crosslinking agents[1].
[1]. Andrew F. Voter, et al. A high throughput screening strategy to identify protein-protein interaction inhibitors that block the Fanconi anemia DNA repair pathway. J Biomol Screen. 2016 Jul; 21(6): 626-633.