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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Publicado en:Nat Commun
Main Authors: 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.
Formato: Artigo
Idioma:Inglês
Publicado: Nature Publishing Group UK 2021
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Article
Acceso en liña: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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