1558598-41-6

PFM01, N-alkylated Mirin derivative, is a MRE11 endonuclease inhibitor. PFM01 can regulate double-strand break repair (DSBR) by nonhomologous end-joining (NHEJ) versus homologous recombination (HR)[1][2].

PFM01 is a cell-permeable N-alkylated Mirin (Sigma Cat. No. 475954) derivative that selectively inhibits against MRE11 endo-, but not exo-, nuclease activity. PFM01 targets MRE11 at a site near the dimer interface, distinct from that occupied by Mirin and PFM39 to allow disruption of the ssDNA-binding groove and selective inhibition against MRE11 endo-, but not exo-, nuclease activity. While both endonuclease and exonuclease activities are required for MRE11-mediated homologous recombination (HR) repair, only FM01 (100 μM), but not the exonuclease inhibitors Mirin (500 μM) and PFM39 (100 μM), rescues G2-phase double-strand break (DSB) repair defect in HR protein BRCA2-deficient HSC62-hTERT fibroblasts following ionizing irradiation (IR) by blocking HR initiation and thereby allowing non-homologous end joining (NHEJ) to proceed.

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[1] Shibata A, et, al. DNA double-strand break repair pathway choice is directed by distinct MRE11 nuclease activities. Mol Cell. 2014 Jan 9; 53(1): 7-18. DOI:10.1016/j.molcel.2013.11.003
[2] V?lkening L, et, al. RAD50 regulates mitotic progression independent of DNA repair functions. FASEB J. 2020 Feb; 34(2): 2812-2820. DOI:10.1096/fj.201902318R