1325757-35-4Relevant academic research and scientific papers
REPLICATION PROTEIN A (RPA)-DNA INTERACTION INHIBITORS
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Paragraph 0169; 0176; 0177, (2021/06/22)
This invention relates to RPA compounds or pharmaceutically acceptable salts thereof, and for the use of the compounds to treat cancer.
Structure-Guided Optimization of Replication Protein A (RPA)-DNA Interaction Inhibitors
Gavande, Navnath S.,Gavande, Navnath S.,Vandervere-Carozza, Pamela S.,Pawelczak, Katherine S.,Vernon, Tyler L.,Jordan, Matthew R.,Turchi, John J.,Turchi, John J.,Turchi, John J.
, p. 1118 - 1124 (2020/02/06)
Replication protein A (RPA) is the major human single stranded DNA (ssDNA)-binding protein, playing essential roles in DNA replication, repair, recombination, and DNA-damage response (DDR). Inhibition of RPA-DNA interactions represents a therapeutic strategy for cancer drug discovery and has great potential to provide single agent anticancer activity and to synergize with both common DNA damaging chemotherapeutics and newer targeted anticancer agents. In this letter, a new series of analogues based on our previously reported TDRL-551 (4) compound were designed to improve potency and physicochemical properties. Molecular docking studies guided molecular insights, and further SAR exploration led to the identification of a series of novel compounds with low micromolar RPA inhibitory activity, increased solubility, and excellent cellular up-take. Among a series of analogues, compounds 43, 44, 45, and 46 hold promise for further development of novel anticancer agents.
MATERIALS AND METHOD FOR INHIBITING REPLICATION PROTEIN A AND USES THEREOF
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Paragraph 00110; 00115, (2016/06/06)
Targeting uncontrolled cell proliferation and resistance to DNA damaging chemotherapeutics with at least one reagent has significant potential in cancer treatment. Replication Protein A, the eukaryotic single-strand (ss) DNA binding protein, is essential for genomic maintenance and stability via roles in both DNA replication and repair. Reported herein are small molecules that inhibit the in vitro, in vivo, and cellular ssDNA binding activity of RPA, thereby disrupting the eukaryotic cell cycle, inducing cytotoxicity and increasing the efficacy of chemotherapeutic agents damage DNA, and/or disrupt its replication and/or function. These results provide new insights into the mechanism of RPA-ssDNA interactions in chromosome maintenance and stability. This represents a molecularly targeted eukaryotic DNA binding inhibitor and demonstrates the utility of targeting a protein-DNA interaction as a means of studying the cell cycle and providing a therapeutic strategy for cancer treatment.
MATERIALS AND METHOD FOR INHIBITING REPLICATION PROTEIN A AND USES THEREOF
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Page/Page column 8-9, (2011/09/14)
Targeting uncontrolled cell proliferation and resistance to DNA damaging chemotherapeutics with at least one reagent has significant potential in cancer treatment. Replication Protein A, the eukaryotic single-strand (ss) DNA binding protein, is essential
