Mostra el registre parcial de l'element
dc.contributor.author | Antolín Hernández, Albert, 1984- |
dc.contributor.author | Mestres i López, Jordi |
dc.date.accessioned | 2020-12-01T08:02:55Z |
dc.date.available | 2020-12-01T08:02:55Z |
dc.date.issued | 2014 |
dc.identifier.citation | Antolín AA, Mestres J. Linking off-target kinase pharmacology to the differential cellular effects observed among PARP inhibitors. Oncotarget. 2014; 5(10):3023-8. DOI: 10.18632/oncotarget.1814 |
dc.identifier.issn | 1949-2553 |
dc.identifier.uri | http://hdl.handle.net/10230/45917 |
dc.description.abstract | PARP inhibitors hold promise as a novel class of targeted anticancer drugs. However, their true mechanism of action is still not well understood following recent reports that show marked differences in cellular effects. Here, we demonstrate that three PARP drug candidates, namely, rucaparib, veliparib, and olaparib, have a clearly different in vitro affinity profile across a panel of diverse kinases selected using a computational approach that relates proteins by ligand similarity. In this respect, rucaparib inhibits nine kinases with micromolar affinity, including PIM1, PIM2, PRKD2, DYRK1A, CDK1, CDK9, HIPK2, CK2, and ALK. In contrast, olaparib does not inhibit any of the sixteen kinases tested. In between, veliparib inhibits only two, namely, PIM1 and CDK9. The differential kinase pharmacology observed among PARP inhibitors provides a plausible explanation to their different cellular effects and offers unexplored opportunities for this drug class, but alerts also on the risk associated to transferring directly both preclinical and clinical outcomes from one PARP drug candidate to another. |
dc.description.sponsorship | This research was funded by the Catalan Government grant 2013FIB2-00073 to A.A. Antolín, and the Spanish Ministerio de Economía y Competitividad grant BIO2011-26669 to J. Mestres. |
dc.format.mimetype | application/pdf |
dc.language.iso | eng |
dc.publisher | Impact Journals |
dc.relation.ispartof | Oncotarget. 2014; 5(10):3023-8 |
dc.rights | This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/ |
dc.title | Linking off-target kinase pharmacology to the differential cellular effects observed among PARP inhibitors |
dc.type | info:eu-repo/semantics/article |
dc.identifier.doi | http://dx.doi.org/10.18632/oncotarget.1814 |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/3PN/BIO2011-26669 |
dc.rights.accessRights | info:eu-repo/semantics/openAccess |
dc.type.version | info:eu-repo/semantics/publishedVersion |