2019
Structural and pharmacological evaluation of a novel non-nucleoside reverse transcriptase inhibitor as a promising long acting nanoformulation for treating HIV
Kudalkar SN, Ullah I, Bertoletti N, Mandl HK, Cisneros JA, Beloor J, Chan AH, Quijano E, Saltzman WM, Jorgensen WL, Kumar P, Anderson KS. Structural and pharmacological evaluation of a novel non-nucleoside reverse transcriptase inhibitor as a promising long acting nanoformulation for treating HIV. Antiviral Research 2019, 167: 110-116. PMID: 31034849, PMCID: PMC6554724, DOI: 10.1016/j.antiviral.2019.04.010.Peer-Reviewed Original ResearchConceptsCombination antiretroviral therapyBALB/c miceHIV-1C miceT cellsHuman immunodeficiency virus type 1 (HIV-1) infectionImmune deficiency syndrome (AIDS) patientsAntiviral activityNon-nucleoside reverse transcriptase inhibitorNovel non-nucleoside reverse transcriptase inhibitorVirus type 1 infectionDrug-resistant HIV-1Observed serum concentrationsHIV-1 infectionType 1 infectionReverse transcriptase inhibitorNon-nucleoside reversePotent antiviral activityHIV therapeutic agentsSignificant antiviral activitySerum residence timeHIV-1 NNRTIsAntiretroviral therapyClinical benefitSerum concentrations
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