Dataset Information

Identification and Optimization of Anthranilic Acid Based Inhibitors of Replication Protein?A.

ABSTRACT: Replication protein?A (RPA) is an essential single-stranded DNA (ssDNA)-binding protein that initiates the DNA damage response pathway through protein-protein interactions (PPIs) mediated by its 70N domain. The identification and use of chemical probes that can specifically disrupt these interactions is important for validating RPA as a cancer target. A high-throughput screen (HTS) to identify new chemical entities was conducted, and 90 hit compounds were identified. From these initial hits, an anthranilic acid based series was optimized by using a structure-guided iterative medicinal chemistry approach to yield a cell-penetrant compound that binds to RPA70N with an affinity of 812?nm. This compound, 2-(3- (N-(3,4-dichlorophenyl)sulfamoyl)-4-methylbenzamido)benzoic acid (20?c), is capable of inhibiting PPIs mediated by this domain.

SUBMITTER: Patrone JD

PROVIDER: S-EPMC4838552 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Publications

Identification and Optimization of Anthranilic Acid Based Inhibitors of Replication Protein A.

Patrone James D JD Pelz Nicholas F NF Bates Brittney S BS Souza-Fagundes Elaine M EM Vangamudi Bhavatarini B Camper Demarco V DV Kuznetsov Alexey G AG Browning Carrie F CF Feldkamp Michael D MD Frank Andreas O AO Gilston Benjamin A BA Olejniczak Edward T ET Rossanese Olivia W OW Waterson Alex G AG Chazin Walter J WJ Fesik Stephen W SW

ChemMedChem 20160108 8

Replication protein A (RPA) is an essential single-stranded DNA (ssDNA)-binding protein that initiates the DNA damage response pathway through protein-protein interactions (PPIs) mediated by its 70N domain. The identification and use of chemical probes that can specifically disrupt these interactions is important for validating RPA as a cancer target. A high-throughput screen (HTS) to identify new chemical entities was conducted, and 90 hit compounds were identified. From these initial hits, an ...[more]

PMID: 26748787

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Dataset Information

Identification and Optimization of Anthranilic Acid Based Inhibitors of Replication Protein?A.

Publications

Identification and Optimization of Anthranilic Acid Based Inhibitors of Replication Protein A.

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