Towards small molecule inhibitors of mono-ADP-ribosyltransferases
2015 (English)In: European Journal of Medicinal Chemistry, ISSN 0223-5234, E-ISSN 1768-3254, Vol. 95, 546-551 p.Article in journal (Refereed) Published
Protein ADP-ribosylation is a post-translational modification involved in DNA repair, protein degradation, transcription regulation, and epigenetic events. Intracellular ADP-ribosylation is catalyzed predominantly by ADP-ribosyltransferases with diphtheria toxin homology (ARTDs). The most prominent member of the ARTD family, poly(ADP-ribose) polymerase-1 (ARTD1/PARP1) has been a target for cancer drug development for decades. Current PARP inhibitors are generally non-selective, and inhibit the mono-ADP-ribosyltransferases with low potency. Here we describe the synthesis of acylated amino benzamides and screening against the mono-ADP-ribosyltransferases ARTD7/PARP15, ARTD8/PARP14, ARTD10/PARP10, and the poly-ADP-ribosyltransferase ARTD1/PARP1. The most potent compound inhibits ARTD10 with sub-micromolar IC50.
Place, publisher, year, edition, pages
2015. Vol. 95, 546-551 p.
Mono-ADP-ribosyltransferase, mART, Poly(ADP-ribose) polymerase, Diphtheria toxin-like ADP-ribosyltransferase, ARTD inhibitor, PARP inhibitor
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
IdentifiersURN: urn:nbn:se:umu:diva-106136DOI: 10.1016/j.ejmech.2015.03.067ISI: 000354139900046PubMedID: 25847771OAI: oai:DiVA.org:umu-106136DiVA: diva2:841501
FunderSwedish Research Council, 2012-5247Swedish Foundation for Strategic Research , RBc08-0014