dc.contributor.authorQvortrup, Katrine
dc.contributor.authorJensen, Jakob F.
dc.contributor.authorSørensen, Mikael S.
dc.contributor.authorKouskoumvekaki, Irene
dc.contributor.authorPetersen, Rasmus K.
dc.contributor.authorTaboureau, Olivier
dc.contributor.authorKristiansen, Karsten
dc.contributor.authorNielsen, Thomas Eiland
dc.contributor.editorCavalli, Andrea*
dc.identifier.citationQvortrup, K., Jensen, J. F., Sørensen, M. S., Kouskoumvekaki, I., Petersen, R. K., Taboureau, O., et al. (2017). Synthesis and biological evaluation of dihydropyrano-[2,3-c]pyrazoles as a new class of PPARγ partial agonists. PLOS ONE, 12(2), e0162642-.en_US
dc.description.abstractPeroxisome proliferator-activated receptor γ (PPARγ) is a well-known target for thiazolidinedione antidiabetic drugs. In this paper, we present the synthesis and biological evaluation of a series of dihydropyrano[2,3-c]pyrazole derivatives as a novel family of PPARγ partial agonists. Two analogues were found to display high affinity for PPARγ with potencies in the micro molar range. Both of these hits were selective against PPARγ, since no activity was measured when tested against PPARα, PPARδ and RXRα. In addition, a novel modelling approach based on multiple individual flexible alignments was developed for the identification of ligand binding interactions in PPARγ. In combination with cell-based transactivation experiments, the flexible alignment model provides an excellent analytical tool to evaluate and visualize the effect of ligand chemical structure with respect to receptor binding mode and biological activity.en_US
dc.format.extent19 p.en_US
dc.relation.ispartofseriesPLOS ONEen_US
dc.rights© 2017 Qvortrup et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.subjectPartial agonistsen_US
dc.titleSynthesis and biological evaluation of dihydropyrano-[2,3-c]pyrazoles as a new class of PPARγ partial agonistsen_US
dc.typeJournal Article
dc.contributor.researchSingapore Centre for Environmental Life Sciences and Engineeringen_US
dc.description.versionPublished versionen_US

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