MU147 is an MRE11 nuclease inhibitor and chemical probe with anticancer activity, exhibiting IC50 values of 3.7 μM and 0.8 μM against the nuclease activity of human MRE11 and the MRN complex, respectively. MU147 inhibits MRE11 exonuclease and endonuclease activities, preventing MRN -dependent DNA end resection and nascent DNA degradation at stalled replication forks in BRCA2-deficient cells. MU147 delays the DNA damage repair process, inhibits homologous recombination and alternative non-homologous end joining, downregulates ionizing radiation- or camptothecin-induced RPA / RPA32 phosphorylation, and reduces survival of BRCA2-deficient cells. MU147 directly binds MRE11 in cells and impairs its recruitment to damage foci. MU147 can be used in cancer-related research [1].
In Vitro, MU147 (66-100 μM; 2 hours) directly binds MRE11 in cells, destabilizes MRE11 in CETSA with an IC50 of 38 μM, and impairs the recruitment and retention of MRE11 at laser-induced DNA damage sites[1]. MU147 (25 μM; 72 h) inhibits MRE11-dependent HR and A-NHEJ double-strand break repair in U2OS and HEK-293T reporter cells[1]. MU147 (25-50 μM) inhibits DNA end resection and RPA32 S4/S8 phosphorylation in CPT -exposed U2OS cells, with an IC50 of 19 μM for RPA32 pS4/S8 foci, and reduces pRPA S4/S8 and γH2AX immunoblot signals[1]. MU147 (25 μM; co-exposure with 4 mM HU for 4 hours) rescues nascent DNA degradation at stalled replication forks in BRCA2-deficient DLD1 cells[1]. MU147 (25 μM; 72 h) selectively impairs the proliferation of DLD1 cells, reduces the survival rate of BRCA2-deficient DLD1 cells, and has minimal effect on the cell cycle of U2OS cells[1]. MU147 (0.18-700 μM; 85 minutes) is a non-covalent MRE11 inhibitor that inhibits the nuclease activity of human MRE11 and the MRN complex with IC50 values of 3.7 μM and 0.8 μM, respectively, and reduces MRN-mediated degradation of circular ssDNA[1]. MU147 (100 μM; 60 minutes) does not directly bind FEN1 in U2OS cells under CETSA conditions[1].
References:
[1]. Nikulenkov F, et al. Discovery of new inhibitors of nuclease MRE11. European journal of medicinal chemistry. 2025 Mar 05;285:117226.
In Vitro, MU147 (66-100 μM; 2 hours) directly binds MRE11 in cells, destabilizes MRE11 in CETSA with an IC50 of 38 μM, and impairs the recruitment and retention of MRE11 at laser-induced DNA damage sites[1]. MU147 (25 μM; 72 h) inhibits MRE11-dependent HR and A-NHEJ double-strand break repair in U2OS and HEK-293T reporter cells[1]. MU147 (25-50 μM) inhibits DNA end resection and RPA32 S4/S8 phosphorylation in CPT -exposed U2OS cells, with an IC50 of 19 μM for RPA32 pS4/S8 foci, and reduces pRPA S4/S8 and γH2AX immunoblot signals[1]. MU147 (25 μM; co-exposure with 4 mM HU for 4 hours) rescues nascent DNA degradation at stalled replication forks in BRCA2-deficient DLD1 cells[1]. MU147 (25 μM; 72 h) selectively impairs the proliferation of DLD1 cells, reduces the survival rate of BRCA2-deficient DLD1 cells, and has minimal effect on the cell cycle of U2OS cells[1]. MU147 (0.18-700 μM; 85 minutes) is a non-covalent MRE11 inhibitor that inhibits the nuclease activity of human MRE11 and the MRN complex with IC50 values of 3.7 μM and 0.8 μM, respectively, and reduces MRN-mediated degradation of circular ssDNA[1]. MU147 (100 μM; 60 minutes) does not directly bind FEN1 in U2OS cells under CETSA conditions[1].
References:
[1]. Nikulenkov F, et al. Discovery of new inhibitors of nuclease MRE11. European journal of medicinal chemistry. 2025 Mar 05;285:117226.