2024
Correction to “Design, Synthesis, and Mechanistic Studies of (R)‑3-Amino-5,5-difluorocyclohex-1-ene-1-carboxylic Acid as an Inactivator of Human Ornithine Aminotransferase”
Devitt A, Vargas A, Zhu W, Des Soye B, Butun F, Alt T, Kaley N, Ferreira G, Moran G, Kelleher N, Liu D, Silverman R. Correction to “Design, Synthesis, and Mechanistic Studies of (R)‑3-Amino-5,5-difluorocyclohex-1-ene-1-carboxylic Acid as an Inactivator of Human Ornithine Aminotransferase”. ACS Chemical Biology 2024, 19: 1850-1850. PMID: 39023367, DOI: 10.1021/acschembio.4c00478.Peer-Reviewed Original ResearchSynthesis of (2R,4S)‑4-Amino-5-hydroxybicyclo[3.1.1]heptane-2-carboxylic Acid via an Asymmetric Intramolecular Mannich Reaction
Dukes A, Weerawarna P, Devitt A, Silverman R. Synthesis of (2R,4S)‑4-Amino-5-hydroxybicyclo[3.1.1]heptane-2-carboxylic Acid via an Asymmetric Intramolecular Mannich Reaction. The Journal Of Organic Chemistry 2024, 89: 9110-9117. PMID: 38857432, PMCID: PMC11418922, DOI: 10.1021/acs.joc.4c00781.Peer-Reviewed Original ResearchDesign, Synthesis, and Mechanistic Studies of (R)‑3-Amino-5,5-difluorocyclohex-1-ene-1-carboxylic Acid as an Inactivator of Human Ornithine Aminotransferase
Devitt A, Vargas A, Zhu W, Soye B, Butun F, Alt T, Kaley N, Ferreira G, Moran G, Kelleher N, Liu D, Silverman R. Design, Synthesis, and Mechanistic Studies of (R)‑3-Amino-5,5-difluorocyclohex-1-ene-1-carboxylic Acid as an Inactivator of Human Ornithine Aminotransferase. ACS Chemical Biology 2024, 19: 1066-1081. PMID: 38630468, PMCID: PMC11274680, DOI: 10.1021/acschembio.4c00022.Peer-Reviewed Original ResearchConceptsActive siteX-ray crystallographyIntact protein mass spectrometryHuman ornithine aminotransferaseNucleophilic additionRing scaffoldMass spectrometryIntermediate speciesProtein mass spectrometryIncreased selectivityTransient state kinetic studiesX-rayMechanistic studiesAdductsSolvent accessibilityKinetic studiesHepatocellular carcinomaProgression of hepatocellular carcinomaMechanism of inactivationStructural evidencePrevalence of hepatocellular carcinomaTreatment of hepatocellular carcinomaCyclohexeneCyclopenteneCrystallographyCrystallographic and Computational Insights into Isoform-Selective Dynamics in Nitric Oxide Synthase
Li H, Hardy C, Reidl C, Jing Q, Xue F, Cinelli M, Silverman R, Poulos T. Crystallographic and Computational Insights into Isoform-Selective Dynamics in Nitric Oxide Synthase. Biochemistry 2024, 63: 788-796. PMID: 38417024, PMCID: PMC10956423, DOI: 10.1021/acs.biochem.3c00601.Peer-Reviewed Original ResearchConceptsHydrogen bondsHeme propionatesDimer interfaceInhibitor bindingCombination of crystallographyInhibitor binding siteDevelopment of isoform-selective inhibitorsIsoform-selective inhibitorsStructural basisComputational insightsStructural changesInhibitor moleculesChanges conformationBinding sitesConformational changesBondsSite inhibitorsPterin cofactorBindingHydrogenSynthaseDimerStructural differencesTyrosineInhibitors
2023
Target Identification of a Class of Pyrazolone Protein Aggregation Inhibitor Therapeutics for Amyotrophic Lateral Sclerosis
Weerawarna P, Schiefer I, Soares P, Fox S, Morimoto R, Melani R, Kelleher N, Luan C, Silverman R. Target Identification of a Class of Pyrazolone Protein Aggregation Inhibitor Therapeutics for Amyotrophic Lateral Sclerosis. ACS Central Science 2023, 10: 87-103. PMID: 38292603, PMCID: PMC10823514, DOI: 10.1021/acscentsci.3c00213.Peer-Reviewed Original ResearchFrom TgO/GABA-AT, GABA, and T-263 Mutant to Conception of Toxoplasma
Lykins J, Moschitto M, Zhou Y, Filippova E, Le H, Tomita T, Fox B, Bzik D, Su C, Rajagopala S, Flores K, Spano F, Woods S, Roberts C, Hua C, Bissati K, Wheeler K, Dovgin S, Muench S, McPhillie M, Fishwick C, Anderson W, Lee P, Hickman M, Weiss L, Dubey J, Lorenzi H, Silverman R, McLeod R. From TgO/GABA-AT, GABA, and T-263 Mutant to Conception of Toxoplasma. IScience 2023, 27: 108477. PMID: 38205261, PMCID: PMC10776954, DOI: 10.1016/j.isci.2023.108477.Peer-Reviewed Original Research
2021
Pregabalin Treatment does not Affect Amyloid Pathology in 5XFAD Mice
Sadleir K, Popovoic J, Zhu W, Reidel C, Do H, Silverman R, Vassar R. Pregabalin Treatment does not Affect Amyloid Pathology in 5XFAD Mice. Current Alzheimer Research 2021, 18: 283-297. PMID: 34259145, PMCID: PMC9527523, DOI: 10.2174/1567205018666210713125333.Peer-Reviewed Original ResearchConceptsVoltagegated calcium channelsPlacebo-treated miceNeuropathic painPregabalin treatmentStatistically significant positive correlationCalcium channelsCalcium influxAb levelsDecreased markersPregabalinSignificant positive correlationCerebral concentrationsEffective treatmentAmyloid depositsCausative roleDystrophyCalcium dysregulationMiceNeuritic dystrophyProgression of amyloid pathologyPathologyImmunofluorescence imagingNeuronal processesPlaqueTreatment
2020
Drug Discovery: Ingenuity and Serendipity...Or is It the Other Way Around?
Silverman R. Drug Discovery: Ingenuity and Serendipity...Or is It the Other Way Around? Annual Reports In Medicinal Chemistry 2020, 1-28. DOI: 10.29200/acsmedchemrev-v55.ch1.Peer-Reviewed Original Research
2016
BASIC SCIENCE TO BLOCKBUSTER DRUG: INVENTION OF PREGABALIN (LYRICA®)
Silverman R. BASIC SCIENCE TO BLOCKBUSTER DRUG: INVENTION OF PREGABALIN (LYRICA®). Technology & Innovation 2016, 17: 153-158. DOI: 10.3727/194982416x14520374942861.Peer-Reviewed Original Research
2014
Preface to the First Edition
Silverman R. Preface to the First Edition. 2014, xiii. DOI: 10.1016/b978-0-12-382030-3.05002-9.Peer-Reviewed Original ResearchChapter 7 Drug Resistance and Drug Synergism
Silverman R, Holladay M. Chapter 7 Drug Resistance and Drug Synergism. 2014, 333-356. DOI: 10.1016/b978-0-12-382030-3.00007-6.Peer-Reviewed Original ResearchDrug synergismReversibility of drug actionDrug actionInhibition of multiple pathwaysEfflux pump inhibitionImproved therapeutic effectMechanisms of resistanceSite of actionPump inhibitionDrug resistanceMultiple drugsTherapeutic effectTarget proteinsProdrug activationDrugDrug targetsDrug distributionMultiple pathwaysInhibitionChapter 9 Prodrugs and Drug Delivery Systems
Silverman R, Holladay M. Chapter 9 Prodrugs and Drug Delivery Systems. 2014, 423-468. DOI: 10.1016/b978-0-12-382030-3.00009-x.Peer-Reviewed Original ResearchChapter 2 Lead Discovery and Lead Modification
Silverman R, Holladay M. Chapter 2 Lead Discovery and Lead Modification. 2014, 19-122. DOI: 10.1016/b978-0-12-382030-3.00002-7.Peer-Reviewed Original ResearchLead compoundsDetermination of structure-activity relationshipsProperties of lead compoundsStages of drug discoveryFragment-based approachConcepts of organic chemistryStructure-activity relationshipVirtual screeningLead discoveryADME propertiesOrganic chemistryGraphics-based methodDrug discoveryCompoundsOral bioavailabilityPharmacophoreComputational methodsPropertiesModification stageChemistryADMELeadChapter 8 Drug Metabolism
Silverman R, Holladay M. Chapter 8 Drug Metabolism. 2014, 357-422. DOI: 10.1016/b978-0-12-382030-3.00008-8.Peer-Reviewed Original ResearchChapter 5 Enzyme Inhibition and Inactivation
Silverman R, Holladay M. Chapter 5 Enzyme Inhibition and Inactivation. 2014, 207-274. DOI: 10.1016/b978-0-12-382030-3.00005-2.Peer-Reviewed Original ResearchChapter 3 Receptors
Silverman R, Holladay M. Chapter 3 Receptors. 2014, 123-163. DOI: 10.1016/b978-0-12-382030-3.00003-9.Peer-Reviewed Original ResearchDrug-receptor interactionsConformational isomersStereochemical featuresRing compoundsMacromolecular receptorsSmall moleculesMolecular forcesMoleculesConcept of topographyTarget receptorsAtropisomersDiastereomersStereochemistryEnantiomersIsomersPartial agonismDrug targetsReceptor agonismRingCompoundsInverse agonismReceptor bindingReceptorsChapter 6 DNA-Interactive Agents
Silverman R, Holladay M. Chapter 6 DNA-Interactive Agents. 2014, 275-331. DOI: 10.1016/b978-0-12-382030-3.00006-4.Peer-Reviewed Original ResearchPreface to the Third Edition
Silverman R, Silverman R, Holladay M. Preface to the Third Edition. 2014, xvii-xviii. DOI: 10.1016/b978-0-12-382030-3.05001-7.Peer-Reviewed Original ResearchChapter 4 Enzymes
Silverman R, Holladay M. Chapter 4 Enzymes. 2014, 165-205. DOI: 10.1016/b978-0-12-382030-3.00004-0.Peer-Reviewed Original ResearchChapter 1 Introduction
Silverman R, Holladay M. Chapter 1 Introduction. 2014, 1-17. DOI: 10.1016/b978-0-12-382030-3.00001-5.Peer-Reviewed Original Research