216880-68-1Relevant academic research and scientific papers
Discovery of protein-protein interaction inhibitors of replication protein A
Patrone, James D.,Kennedy, J. Phillip,Frank, Andreas O.,Feldkamp, Michael D.,Vangamudi, Bhavatarini,Pelz, Nicholas F.,Rossanese, Olivia W.,Waterson, Alex G.,Chazin, Walter J.,Fesik, Stephen W.
, p. 601 - 605 (2013/07/26)
Replication protein A (RPA) is a ssDNA binding protein that is essential for DNA replication and repair. The initiation of the DNA damage response by RPA is mediated by protein-protein interactions involving the N-terminal domain of the 70 kDa subunit with partner proteins. Inhibition of these interactions increases sensitivity toward DNA damage and replication stress and may therefore be a potential strategy for cancer drug discovery. Toward this end, we 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 may offer a promising starting point for the discovery of clinically useful RPA inhibitors.
