biostudies-literatureGlanzer JGNCRR NIH HHS2589-95https://www.ebi.ac.uk/biostudies/studies/S-EPMC3399738biostudies-literatureUnknown19(8)The pharmacological suppression of the DNA damage response and DNA repair can increase the therapeutic indices of conventional chemotherapeutics. Replication Protein A (RPA), the major single-stranded DNA binding protein in eukaryotes, is required for DNA replication, DNA repair, DNA recombination, and DNA damage response signaling. Through the use of high-throughput screening of 1500 compounds, we have identified a small molecule inhibitor, 15-carboxy-13-isopropylatis-13-ene-17,18-dioic acid (NSC15520), that inhibited both the binding of Rad9-GST and p53-GST fusion proteins to the RPA N-terminal DNA binding domain (DBD), interactions that are essential for robust DNA damage signaling. NSC15520 competitively inhibited the binding of p53-GST peptide with an IC(50) of 10 μM. NSC15520 also inBioorganic & medicinal chemistrySmall molecule inhibitor of the RPA70 N-terminal protein interaction domain discovered using in silico and in vitro methods.PMC3399738P20 RR018759P20-RR01875Oakley GGGlanzer JGLiu SfalseSmall molecule inhibitor of the RPA70 N-terminal protein interaction domain discovered using in silico and in vitro methods.The pharmacological suppression of the DNA damage response and DNA repair can increase the therapeutic indices of conventional chemotherapeutics. Replication Protein A (RPA), the major single-stranded DNA binding protein in eukaryotes, is required for DNA replication, DNA repair, DNA recombination, and DNA damage response signaling. Through the use of high-throughput screening of 1500 compounds, we have identified a small molecule inhibitor, 15-carboxy-13-isopropylatis-13-ene-17,18-dioic acid (NSC15520), that inhibited both the binding of Rad9-GST and p53-GST fusion proteins to the RPA N-terminal DNA binding domain (DBD), interactions that are essential for robust DNA damage signaling. NSC15520 competitively inhibited the binding of p53-GST peptide with an IC(50) of 10 μM. NSC15520 also in2011-01-01T00:00:00Z2011 Apr2026-04-29T06:50:09.996Z2026-04-14T03:07:03.993ZS-EPMC33997382145900110.1016/j.bmc.2011.03.012