Polθ inhibitors elicit BRCA-gene synthetic lethality and target PARP inhibitor resistance

To identify approaches to target DNA repair vulnerabilities in cancer, we discovered nanomolar potent, selective, low molecular weight (MW), allosteric inhibitors of the polymerase function of DNA polymerase Polθ, including ART558. ART558 inhibits the major Polθ-mediated DNA repair process, Theta-Me...

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Veröffentlicht in:Nat Commun
Hauptverfasser: Zatreanu, Diana, Robinson, Helen M. R., Alkhatib, Omar, Boursier, Marie, Finch, Harry, Geo, Lerin, Grande, Diego, Grinkevich, Vera, Heald, Robert A., Langdon, Sophie, Majithiya, Jayesh, McWhirter, Claire, Martin, Niall M. B., Moore, Shaun, Neves, Joana, Rajendra, Eeson, Ranzani, Marco, Schaedler, Theresia, Stockley, Martin, Wiggins, Kimberley, Brough, Rachel, Sridhar, Sandhya, Gulati, Aditi, Shao, Nan, Badder, Luned M., Novo, Daniela, Knight, Eleanor G., Marlow, Rebecca, Haider, Syed, Callen, Elsa, Hewitt, Graeme, Schimmel, Joost, Prevo, Remko, Alli, Christina, Ferdinand, Amanda, Bell, Cameron, Blencowe, Peter, Bot, Chris, Calder, Mathew, Charles, Mark, Curry, Jayne, Ekwuru, Tennyson, Ewings, Katherine, Krajewski, Wojciech, MacDonald, Ellen, McCarron, Hollie, Pang, Leon, Pedder, Chris, Rigoreau, Laurent, Swarbrick, Martin, Wheatley, Ed, Willis, Simon, Wong, Ai Ching, Nussenzweig, Andre, Tijsterman, Marcel, Tutt, Andrew, Boulton, Simon J., Higgins, Geoff S., Pettitt, Stephen J., Smith, Graeme C. M., Lord, Christopher J.
Format: Artigo
Sprache:Inglês
Veröffentlicht: Nature Publishing Group UK 2021
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Online Zugang:https://ncbi.nlm.nih.gov/pmc/articles/PMC8211653/
https://ncbi.nlm.nih.gov/pubmed/34140467
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1038/s41467-021-23463-8
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