Bractoppin is a potent and selective inhibitor of phosphopeptide recognition by the human BRCA1 tandem BRCT domain (IC50: 74 nM). It reduces BRCA1 recruitment to DNA breaks, thereby suppressing damage-induced G2 arrest and assembly of the recombinase, RAD51. Bractoppin predominantly inhibits BRCA1 tBRCT-dependent processes in the DNA damage response[1].
体外研究
In an MST assay, Bractoppin demonstrates nanomolar potency in displacing the cognate BACH1 phosphopeptide substrate from the BRCA1 tBRCT, with a binding IC50 value of 74 nM[1].
In a selectivity profile assessed through competitive MST assay, Bractoppin (0-100 μM) shows no observable binding to fluorescently labeled tBRCT domains from MCPH1, TOPBP1 7/8, ECT2, or TOPBP1 1/2[1].
Bractoppin (100μM) selectively suppresses damage-induced BRCA1 foci formation, while it has minimal impact on the radiation-induced accumulation of MDC1 at DNA damage sites. Similarly, Bractoppin shows negligible influence on the radiation-induced recruitment of TOPBP1 (a protein containing multiple, structurally related tBRCT domains)[1].
Bractoppin (10-100 μM; 0.5 hr before radiation (32 hours)) dose-dependently suppresses 4Gy radiation-induced G2 arrest. The percentage of G2-arrested cells decreases to 64%, 42%, and 25% for 10 μM, 30 μM, and 100 μM, respectively[1].
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