Bractoppin

Bractoppin is a potent and selective drug-like inhibitor of phosphopeptide recognition by the human BRCA1 tandem(t) BRCT domain (binding IC₅₀: 74 nM). Bractoppin diminishes BRCA1 recruitment to DNA breaks, in turn suppressing damage-induced G2 arrest and assembly of the recombinase, RAD51. Bractoppin preferentially inhibits BRCA1 tBRCT-dependent steps in the DNA damage response^[1]. In Vitro: In a MST assay, Bractoppin exhibits nanomolar potency in displacing cognate BACH1 phosphopeptide substrate from the BRCA1 tBRCT, the binding IC₅₀ value is 74 nM^[1].
In a selectivity profile by competitive MST assay, Bractoppin (0-100 μM) does not detectably bind to fluorescently labeled tBRCT domains from MCPH1, TOPBP1 7/8, ECT2, or TOPBP1 1/2^[1].
Bractoppin (100 μM) selectively inhibits damage-induced BRCA1 foci formation, but has little effect on the radiation-induced accumulation of MDC1 at sites of DNA damage. Similarly, Bractoppin has little effect 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)) inhibits 4Gy radiation induced G2 arrest in a dose-dependent manner. The percentage of G2 arrest cell is 64%, 42% and 25% for 10 μM, 30 μM and 100 μM, respectively^[1].