Featured Publications
New Insights into Human 17β-Hydroxysteroid Dehydrogenase Type 14: First Crystal Structures in Complex with a Steroidal Ligand and with a Potent Nonsteroidal Inhibitor
Bertoletti N, Braun F, Lepage M, Möller G, Adamski J, Heine A, Klebe G, Marchais-Oberwinkler S. New Insights into Human 17β-Hydroxysteroid Dehydrogenase Type 14: First Crystal Structures in Complex with a Steroidal Ligand and with a Potent Nonsteroidal Inhibitor. Journal Of Medicinal Chemistry 2016, 59: 6961-6967. PMID: 27362750, DOI: 10.1021/acs.jmedchem.6b00293.Peer-Reviewed Original ResearchConceptsCrystal structureStructure-based inhibitor designFirst crystal structureNonsteroidal inhibitorsPotent nonsteroidal inhibitorSDR enzymesInhibitor designHolo formHuman enzymeNatural variantsSteroidal ligandsTernary complexNew insightsComplexesSimilar structureEnzymeStructureType 14InhibitorsLigandsVariants
2018
Structure-based design and profiling of novel 17β-HSD14 inhibitors
Braun F, Bertoletti N, Möller G, Adamski J, Frotscher M, Guragossian N, Gírio P, Le Borgne M, Ettouati L, Falson P, Müller S, Vollmer G, Heine A, Klebe G, Marchais-Oberwinkler S. Structure-based design and profiling of novel 17β-HSD14 inhibitors. European Journal Of Medicinal Chemistry 2018, 155: 61-76. PMID: 29859505, DOI: 10.1016/j.ejmech.2018.05.029.Peer-Reviewed Original ResearchConceptsCrystal structureChemical probesStructure-based optimizationStructure-based designInhibitor-enzyme complexGood selectivity profilePromising chemical probeGood solubilityCompound 1Hydroxyl groupsSubstitution patternPhysiological roleSelectivity profileTarget enzymeNonsteroidal inhibitorsPosition 17EnzymeEstrogen receptor alphaReceptor alphaCompoundsPotent inhibitorInhibitory activityProfilingInhibitorsHighest inhibition
2016
First Structure–Activity Relationship of 17β-Hydroxysteroid Dehydrogenase Type 14 Nonsteroidal Inhibitors and Crystal Structures in Complex with the Enzyme
Braun F, Bertoletti N, Möller G, Adamski J, Steinmetzer T, Salah M, Abdelsamie A, van Koppen C, Heine A, Klebe G, Marchais-Oberwinkler S. First Structure–Activity Relationship of 17β-Hydroxysteroid Dehydrogenase Type 14 Nonsteroidal Inhibitors and Crystal Structures in Complex with the Enzyme. Journal Of Medicinal Chemistry 2016, 59: 10719-10737. PMID: 27933965, DOI: 10.1021/acs.jmedchem.6b01436.Peer-Reviewed Original ResearchConceptsStructure-activity relationshipsExtended H-bonding networkH-bonding networkFirst structure-activity relationshipsLigand-based approachesEnzyme active siteCrystallographic structure analysisNonsteroidal inhibitorsScaffold diversityChemical modificationHydroxyl groupsActive siteCrystal structureInteresting hitsPotent compoundsStrong affinityStructure analysisBest inhibitorCompoundsInhibitory activitySDR familyStabilization processHigh affinityAffinitySelectivity