Replication protein A (RPA) is often a ssDNA binding protein that is certainly important for DNA replication and fix. The initiation from the DNA damage biological activity response sellectchem by RPA is mediated by protein protein interactions involving the N-terminal domain with the 70 kDa subunit with companion proteins. Inhibition of those interactions increases sensitivity toward DNA harm and replication stress and may possibly thus be a likely system for cancer drug Tamoxifen discovery. Towards this end, we now have discovered two lead series of compounds, derived from hits obtained from a fragment-based screen that bind to RPA70N with low micromolar affinity and inhibit the binding of an ATRIP-derived peptide to RPA. These compounds might provide a promising starting up point for the discovery of clinically helpful RP inhibitors.