Ontology highlight
ABSTRACT:
SUBMITTER: Kossmann BR
PROVIDER: S-EPMC4939481 | biostudies-literature | 2016 Jul
REPOSITORIES: biostudies-literature
Kossmann Bradley R BR Abdelmalak Monica M Lopez Sophia S Tender Gabrielle G Yan Chunli C Pommier Yves Y Marchand Christophe C Ivanov Ivaylo I
Bioorganic & medicinal chemistry letters 20160524 14
Tyrosyl-DNA phosphodiesterase 2 (TDP2) processes protein/DNA adducts resulting from abortive DNA topoisomerase II (Top2) activity. TDP2 inhibition could provide synergism with the Top2 poison class of chemotherapeutics. By virtual screening of the NCI diversity small molecule database, we identified selective TDP2 inhibitors and experimentally verified their selective inhibitory activity. Three inhibitors exhibited low-micromolar IC50 values. Molecular dynamics simulations revealed a common bind ...[more]