2025
High-throughput multiplex voltage-clamp/current-clamp evaluation of acutely isolated neurons
Ghovanloo M, Tyagi S, Zhao P, Kiziltug E, Estacion M, Effraim P, Dib-Hajj S, Waxman S. High-throughput multiplex voltage-clamp/current-clamp evaluation of acutely isolated neurons. Nature Protocols 2025, 1-26. PMID: 40514421, DOI: 10.1038/s41596-025-01194-0.Peer-Reviewed Original ResearchPatch-clamp techniquePatch-clamp methodPatch-clamp approachPatch-clamp experimentsHeterologous cell linesIsolated neuronsInvestigated receptorsGraphical user interfaceIsolation of neuronsCell preparationsExcitable cellsOpen-source softwareCell linesNeuronsFiltration criteriaIndividual neuronsUser interfaceNative stateDrug screeningRobotic systemDrug developmentManual implementationBiophysical equationsComplex datasetsIntact tissueStructural insights into RNA targeting with de novo small molecule
Xu L, Chung K, Liu T, Pyle A. Structural insights into RNA targeting with de novo small molecule. Structural Dynamics 2025, 12: a41-a41. DOI: 10.1063/4.0000350.Peer-Reviewed Original ResearchRNA-small molecule interactionsChemical space explorationRNA-ligand recognitionMedicinal chemistry campaignHigh-throughput screening assayChemistry campaignSelf-splicing intronsInhibitor discoveryNon-coding genesMolecule interactionsCryo-EM structureSmall moleculesAtomic detailRNA bindersStructural insightsMolecular interactionsC. albicansTarget RNASplicing inhibitorsGene productsRNA moleculesRNA targetsDruggable genomeDrug developmentMoleculesAdvancing drug development in myelodysplastic syndromes
Mina A, McGraw K, Cunningham L, Kim N, Jen E, Calvo K, Ehrlich L, Aplan P, Garcia-Manero G, Foran J, Garcia J, Zeidan A, DeZern A, Komrokji R, Sekeres M, Scott B, Buckstein R, Tinsley-Vance S, Verma A, Wroblewski T, Pavletic S, Norsworthy K. Advancing drug development in myelodysplastic syndromes. Blood Advances 2025, 9: 1095-1104. PMID: 39786387, PMCID: PMC11914162, DOI: 10.1182/bloodadvances.2024014865.Peer-Reviewed Original ResearchConceptsAllogeneic hematopoietic stem cell transplantationHematopoietic stem cell transplantationEnd pointsStem cell malignanciesTime-to-event end pointsStem cell transplantationUS Food and Drug AdministrationTreatment of patientsFood and Drug AdministrationClinical trial designDrug developmentMyelodysplastic syndromeCell transplantationCurative therapyRisk stratificationPoor prognosisCell malignancyTransformative therapiesDrug AdministrationBiomarker developmentResponse definitionsTrial designFunctional assessmentTherapyPatientsVoltage-gated sodium channels in excitable cells as drug targets
Alsaloum M, Dib-Hajj S, Page D, Ruben P, Krainer A, Waxman S. Voltage-gated sodium channels in excitable cells as drug targets. Nature Reviews Drug Discovery 2025, 24: 358-378. PMID: 39901031, DOI: 10.1038/s41573-024-01108-x.Peer-Reviewed Original ResearchSodium channelsChannel subtypesControl action potential firingDevelopment of drugsDensity of voltage-gated sodiumExcitable cellsAction potential firingSubtype-specific drugsSodium channel subtypesVoltage-gated sodium channelsExpressing high densitiesVoltage-gated sodiumCardiac myocytesNav1.1-Nav1.9Potential firingCardiac disordersAction potentialsMuscle cellsMolecular targetsDrugSubtypesDrug developmentCellsDrug targetsMyocytesExploring Possible Drug-Resistant Variants of SARS-CoV‑2 Main Protease (Mpro) with Noncovalent Preclinical Candidate, Mpro61
Kenneson J, Papini C, Tang S, Huynh K, Zhang C, Jorgensen W, Anderson K. Exploring Possible Drug-Resistant Variants of SARS-CoV‑2 Main Protease (Mpro) with Noncovalent Preclinical Candidate, Mpro61. ACS Bio & Med Chem Au 2025, 5: 215-226. PMID: 39990941, PMCID: PMC11843330, DOI: 10.1021/acsbiomedchemau.4c00109.Peer-Reviewed Original ResearchDrug resistance mutationsViral passaging experimentsDrug-resistant clinical isolatesCOVID infectionDrug-resistant variantsSARS-CoV-2 MClinical isolatesPassage experimentsIncreased up to 10-foldClinical useSARS-CoV-2 main proteaseWild typePreclinical candidateDouble variantInhibitorsMutationsDrug developmentInfectionNirmatrelvirMain proteaseProlonged usageMedicinal chemistry modificationsVariantsTarget-based approachPatientsChapter 49 Phase 0 & window of opportunity clinical trials
Reddy A, Bansal U, Lerner S. Chapter 49 Phase 0 & window of opportunity clinical trials. 2025, 249-253. DOI: 10.1016/b978-0-323-90186-4.00009-2.Peer-Reviewed Original ResearchExploratory investigational new drugClinical trialsPhase 1 clinical trialPreclinical animal studiesFood and Drug AdministrationInvestigational new drugOn-target effectsPhase 0 studiesDrug pharmacokineticsDrug efficacyDrug AdministrationAnimal studiesOncology drugsDrug trialsSuboptimal pharmacological propertiesNew drugsDrug approvalDrugDrug approval processCosts associated with drug developmentPharmacological propertiesDrug safetyTrialsDrug developmentTherapeutic areas
2024
Optimizing public-private partnerships to support clinical cancer research
Herbst R, Blumenthal G, Khleif S, Lippman S, Meropol N, Rosati K, Shulman L, Smith H, Wang M, Winn R, Schilsky R. Optimizing public-private partnerships to support clinical cancer research. Journal Of The National Cancer Institute 2024, djae279. PMID: 39666955, DOI: 10.1093/jnci/djae279.Peer-Reviewed Original ResearchClinical cancer researchNational Cancer Policy ForumPublic-private partnershipEquitable care deliveryCancer researchCare deliveryEfficient drug developmentImplementation of public-private partnershipPromote collaborationTherapeutic innovationsClinical applicationPartnershipPolicy forumsDrug developmentNonprofit organizationsA brave new framework for glioma drug development
Hotchkiss K, Karschnia P, Schreck K, Geurts M, Cloughesy T, Huse J, Duke E, Lathia J, Ashley D, Nduom E, Long G, Singh K, Chalmers A, Ahluwalia M, Heimberger A, Bagley S, Todo T, Verhaak R, Kelly P, Hervey-Jumper S, de Groot J, Patel A, Fecci P, Parney I, Wykes V, Watts C, Burns T, Sanai N, Preusser M, Tonn J, Drummond K, Platten M, Das S, Tanner K, Vogelbaum M, Weller M, Whittle J, Berger M, Khasraw M. A brave new framework for glioma drug development. The Lancet Oncology 2024, 25: e512-e519. PMID: 39362262, PMCID: PMC11983286, DOI: 10.1016/s1470-2045(24)00190-6.Peer-Reviewed Original ResearchConceptsBrain tumorsBenefits of biopsyBrain tumor therapyLiquid biopsy technologiesTissue samplesPostoperative deficitsBiopsy techniqueBiopsy technologyEffective therapySurgical trialsClinical trialsTumor therapyResistance mechanismsTumorTherapyPatientsDrug developmentTissue analysisBrainTrialsTissueBiopsyGliomaRegulatory agenciesQualitative Analysis and Comparison of Externally Led, Patient-Focused Drug Development (EL-PFDD) Concepts for Autosomal Recessive Polycystic Kidney Disease (ARPKD) against Standardized Outcomes in Nephrology (SONG) Initiatives
Soyfer B, Fedeles S, Vanasco W, Perrone R, Liebau M, Hartung E, Dell K, Guay-Woodford L, Hoover E, Oberdhan D. Qualitative Analysis and Comparison of Externally Led, Patient-Focused Drug Development (EL-PFDD) Concepts for Autosomal Recessive Polycystic Kidney Disease (ARPKD) against Standardized Outcomes in Nephrology (SONG) Initiatives. Journal Of The American Society Of Nephrology 2024, 35: 10.1681/asn.2024fj4z3w71. DOI: 10.1681/asn.2024fj4z3w71.Peer-Reviewed Original ResearchA framework for translating tauopathy therapeutics: Drug discovery to clinical trials
Feldman H, Cummings J, Boxer A, Staffaroni A, Knopman D, Rizzo S, Territo P, Arnold S, Ballard C, Beher D, Boeve B, Dacks P, Diaz K, Ewen C, Fiske B, Gonzalez M, Harris G, Hoffman B, Martinez T, McDade E, Nisenbaum L, Palma J, Quintana M, Rabinovici G, Rohrer J, Rosen H, Troyer M, Kim D, Tanzi R, Zetterberg H, Ziogas N, May P, Rommel A. A framework for translating tauopathy therapeutics: Drug discovery to clinical trials. Alzheimer's & Dementia 2024, 20: 8129-8152. PMID: 39316411, PMCID: PMC11567863, DOI: 10.1002/alz.14250.Peer-Reviewed Original ResearchPrimary tauopathiesClinically heterogeneous neurodegenerative diseasesTau protein aggregationHeterogeneous neurodegenerative diseaseSurrogate disease biomarkersTauopathiesProtein aggregationDefinition of rare diseasesAlzheimer's diseaseNeurodegenerative diseasesClinical trialsEarly-phase clinical trialsEarly-phase trialsDisease biomarkersFrontotemporal degenerationDrug developmentProgressive supranuclear palsyDiscovery to clinical trialsSelection of targetsTherapeuticsPharmacodynamic biomarkersProspects for Riboswitches in Drug Development
Mohsen M, Breaker R. Prospects for Riboswitches in Drug Development. Methods And Principles In Medicinal Chemistry 2024, 203-226. DOI: 10.1002/9783527840458.ch8.Peer-Reviewed Original ResearchUntranslated regions of messenger RNAsRegions of messenger RNAsModulate gene expressionBacterial physiologyEngineered riboswitchesSynthetic switchesRNA structureRiboswitch functionRiboswitchUntranslated regionSmall moleculesDrug developmentGene expressionDrug-like small moleculesHuman gene therapy applicationsMessenger RNARNAGene therapy applicationsAntibiotic agentsTargeting ligandsTherapy applicationsProteinMoleculesDrugEvolutionary druggability for low-dimensional fitness landscapes toward new metrics for antimicrobial applications
Guerrero R, Dorji T, Harris R, Shoulders M, Ogbunugafor C. Evolutionary druggability for low-dimensional fitness landscapes toward new metrics for antimicrobial applications. ELife 2024, 12: rp88480. PMID: 38833384, PMCID: PMC11149929, DOI: 10.7554/elife.88480.Peer-Reviewed Original ResearchConceptsDrug targetsAllelic variantsStanding genetic variationEmpirical fitness landscapesFitness landscapeGenetic variationB-lactamasePathogenic variantsTarget proteinsVariant sensitivityB-lactamAllelesDrug-target interactionsPathogensMutationsVariantsDrug environmentMechanistic insightDrug developmentMolecular properties of drugsAntimicrobial applicationsApplication metricsLociVariant variablesPharmacological interventionsEvolutionary druggability for low-dimensional fitness landscapes toward new metrics for antimicrobial applications
Guerrero R, Dorji T, Harris R, Shoulders M, Ogbunugafor C. Evolutionary druggability for low-dimensional fitness landscapes toward new metrics for antimicrobial applications. ELife 2024, 12 DOI: 10.7554/elife.88480.3.Peer-Reviewed Original ResearchDrug targetsAllelic variantsStanding genetic variationEmpirical fitness landscapesFitness landscapeGenetic variationB-lactamasePathogenic variantsTarget proteinsVariant sensitivityB-lactamAllelesDrug-target interactionsPathogensMutationsVariantsDrug environmentMechanistic insightDruggabilityDrug developmentMolecular properties of drugsAntimicrobial applicationsApplication metricsLociVariant variablesPatient-focused drug development in primary sclerosing cholangitis: Insights on patient priorities and involvement in clinical trials
Li M, Pai R, Gomel R, Vyas M, Callif S, Hatchett J, Bowlus C, Lai J. Patient-focused drug development in primary sclerosing cholangitis: Insights on patient priorities and involvement in clinical trials. Hepatology Communications 2024, 8: e0433. PMID: 38727680, PMCID: PMC11093571, DOI: 10.1097/hc9.0000000000000433.Peer-Reviewed Original ResearchConceptsPrimary sclerosing cholangitisClinical trialsSclerosing cholangitisDrug trialsTrial participantsMultivariate logistic regressionAssociated with willingnessInflammatory bowel diseaseLong-term riskReferral of patientsDrug developmentTherapy trialsDisease progressionTrial interestBowel diseasePatient-focused drug developmentTreatment trialsPatientsBiopsy requirementsPruritusPatient interestPredictors of patients' willingnessLogistic regressionCholangitisPatients' willingnessLeveraging generative AI to prioritize drug repurposing candidates for Alzheimer’s disease with real-world clinical validation
Yan C, Grabowska M, Dickson A, Li B, Wen Z, Roden D, Michael Stein C, Embí P, Peterson J, Feng Q, Malin B, Wei W. Leveraging generative AI to prioritize drug repurposing candidates for Alzheimer’s disease with real-world clinical validation. Npj Digital Medicine 2024, 7: 46. PMID: 38409350, PMCID: PMC10897392, DOI: 10.1038/s41746-024-01038-3.Peer-Reviewed Original ResearchGenerative artificial intelligenceDrug repurposing candidatesAlzheimer's diseaseRepurposing candidatesSearch spaceGenerative AIArtificial intelligenceChatGPTAD riskClinical datasetsAssociated with lower AD riskLower AD riskDrug repurposingDrug developmentAlzheimerTreatment of diseasesTechnologyDatasetIntelligenceTherapeutic targeting Tudor domains in leukemia via CRISPR-Scan Assisted Drug Discovery
Chan A, Han L, Delaney C, Wang X, Mukhaleva E, Li M, Yang L, Pokharel S, Mattson N, Garcia M, Wang B, Xu X, Zhang L, Singh P, Elsayed Z, Chen R, Kuang B, Wang J, Yuan Y, Chen B, Chan L, Rosen S, Horne D, Müschen M, Chen J, Vaidehi N, Armstrong S, Su R, Chen C. Therapeutic targeting Tudor domains in leukemia via CRISPR-Scan Assisted Drug Discovery. Science Advances 2024, 10: eadk3127. PMID: 38394203, PMCID: PMC10889360, DOI: 10.1126/sciadv.adk3127.Peer-Reviewed Original ResearchConceptsTudor domainDrug discoveryRibosomal gene expressionMolecular dynamics simulationsDomain-focused CRISPR screeningDe novo drug discoveryCompound dockingAcetyltransferase complexCRISPR screensGenetic approachesLead inhibitorDynamics simulationsStructural genetics approachGene expressionH3K9 acetylationEpigenetic dysregulationSgf29Tile scansLeukemia progressionMultiple cancersDrug developmentDiscoveryH3K9DockingLeukemiaNeuroimaging Biomarkers for Drug Discovery and Development in Schizophrenia
Preller K, Scholpp J, Wunder A, Rosenbrock H. Neuroimaging Biomarkers for Drug Discovery and Development in Schizophrenia. Biological Psychiatry 2024, 96: 666-673. PMID: 38272287, DOI: 10.1016/j.biopsych.2024.01.009.Peer-Reviewed Original ResearchNMDA receptor hypofunctionPsychosis spectrum disordersNeuroimaging data acquisitionField of neuroimagingNegative symptomsPharmacological neuroimagingPositive symptomsReceptor hypofunctionPsychotic disordersNeuroimaging resultsSpectrum disorderNeuroimaging technologiesNeuroimaging biomarkersSchizophreniaNeuroimagingPathophysiology of symptomsDrug developmentDecades of researchTarget engagementClinical drug developmentPredictive biomarkersDisordersSymptomsHealthy volunteersDose selectionNew Treatment Approaches in Non-Muscle-Invasive Bladder Cancer
Kim S, Lerner S. New Treatment Approaches in Non-Muscle-Invasive Bladder Cancer. 2024, 439-456. DOI: 10.1007/978-3-031-68505-7_21.Peer-Reviewed Original ResearchNon-muscle-invasive bladder cancerBladder cancerBCG-unresponsive NMIBCProbability of response to treatmentUS Food and Drug AdministrationNew treatment approachesResponse to treatmentFood and Drug AdministrationNuclear gradeBC casesDrug AdministrationHigh riskTreatment approachesDisease subtypesMorphological appearanceDisease statesCancerDrug developmentTreatment
2023
Exploring novel HIV‐1 reverse transcriptase inhibitors with drug‐resistant mutants: A double mutant surprise
Hollander K, Chan A, Frey K, Hunker O, Ippolito J, Spasov K, Yeh Y, Jorgensen W, Ho Y, Anderson K. Exploring novel HIV‐1 reverse transcriptase inhibitors with drug‐resistant mutants: A double mutant surprise. Protein Science 2023, 32: e4814. PMID: 37861472, PMCID: PMC10659932, DOI: 10.1002/pro.4814.Peer-Reviewed Original ResearchConceptsHIV drug developmentReverse transcriptaseHIV-1 reverse transcriptaseNew RT inhibitorsDrug-resistant mutantsLifelong treatmentHIV-1 reverseRT inhibitorsClinical isolatesPreclinical candidateResistance mutationsResistant variantsSuccessful managementMolecular cloneFirst-generation inhibitorsDrug developmentV106ASame mutationCandidate compoundsGeneration inhibitorsInhibitorsKey targetCatechol diethersDevelopment and Pharmacochemical Characterization Discover a Novel Brain-Permeable HDAC11-Selective Inhibitor with Therapeutic Potential by Regulating Neuroinflammation in Mice
Bai P, Liu Y, Yang L, Ding W, Mondal P, Sang N, Liu G, Lu X, Ho T, Zhou Y, Wu R, Birar V, Wilks M, Tanzi R, Lin H, Zhang C, Li W, Shen S, Wang C. Development and Pharmacochemical Characterization Discover a Novel Brain-Permeable HDAC11-Selective Inhibitor with Therapeutic Potential by Regulating Neuroinflammation in Mice. Journal Of Medicinal Chemistry 2023, 66: 16075-16090. PMID: 37972387, PMCID: PMC12080345, DOI: 10.1021/acs.jmedchem.3c01491.Peer-Reviewed Original ResearchConceptsPositron emission tomographyNeuropathic painHDAC11 inhibitorsInhibition of HDAC11Histone deacetylase 11Pharmacokinetic/pharmacodynamic evaluationNeuroimmune functionMouse modelPharmacological inhibitionBrain uptakeEmission tomographyTherapeutic potentialNeurological indicationsPainTherapeutic targetHDAC11Regulating neuroinflammationNeurological disordersDrug developmentMiceInhibitorsHDAC isoformsCarbon-11Metabolic propertiesBrain
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