2025
Safety, pharmacokinetics, and efficacy of HY-072808 ointment, a novel PDE4 inhibitor, in adolescent and adult patients with mild-to-moderate AD
Yao F, He M, Wang J, Li Y, Zhang Q, Yang J, Wu J, Zhang Q, Zhou R, Zhang M, Meng L, Wu L, Chu Z, Hu W. Safety, pharmacokinetics, and efficacy of HY-072808 ointment, a novel PDE4 inhibitor, in adolescent and adult patients with mild-to-moderate AD. Expert Opinion On Investigational Drugs 2025, 34: 435-447. PMID: 40411316, DOI: 10.1080/13543784.2025.2510671.Peer-Reviewed Original ResearchConceptsMild to moderate ADAnti-atopic dermatitisAdult patientsHealthy subjectsPDE4 inhibitorsPhase I clinical trialWell-tolerated treatmentOpen-label trialDouble-blindPlacebo-controlledSafety profileAdverse eventsEASI scoreClinical developmentPharmacokinetic analysisAtopic dermatitisHealthy individualsPatientsPharmacokineticsDrug concentrationsEczema severityQuality of lifeEfficacyTrialsOintmentMoving Beyond Desensitization to Tolerance in Food Allergy
Flom J, Shreffler W, Perrett K. Moving Beyond Desensitization to Tolerance in Food Allergy. The Journal Of Allergy And Clinical Immunology In Practice 2025, 13: 741-744. PMID: 40010566, DOI: 10.1016/j.jaip.2025.02.014.Peer-Reviewed Original ResearchManagement of IgE-mediated food allergyFood allergyIgE-mediated food allergyStages of clinical developmentSide effect profileMode of deliveryGoal of therapeuticsSustained unresponsivenessDosing regimensDose protocolProactive therapyAllergen-specificClinical developmentActive therapyPatient populationSide effectsTherapyPassive therapyPatient-specificDesensitizationClinical contextPatientsDoseAllergyDegree of protectionCharacterization of sulopenem antimicrobial activity using in vitro time-kill kinetics, synergy, post-antibiotic effect, and sub-inhibitory MIC effect methods against Escherichia coli and Klebsiella pneumoniae isolates
Maher J, Huband M, Lindley J, Rhomberg P, Aronin S, Puttagunta S, Castanheira M. Characterization of sulopenem antimicrobial activity using in vitro time-kill kinetics, synergy, post-antibiotic effect, and sub-inhibitory MIC effect methods against Escherichia coli and Klebsiella pneumoniae isolates. Microbiology Spectrum 2025, 13: e01898-24. PMID: 39907459, PMCID: PMC11878024, DOI: 10.1128/spectrum.01898-24.Peer-Reviewed Original ResearchConceptsUncomplicated urinary tract infectionsPost-antibiotic effectIntra-abdominal infectionsTreatment of urinary tractTime-kill testsMultidrug-resistant pathogensBaseline MICPenem antibioticUrinary tractPAE effectsClinical developmentBroth microdilution susceptibility testingPhase 3 clinical trialsKlebsiella pneumoniae isolatesOral dosing regimenUrinary tract infectionMicrodilution susceptibility testingPAE-SMETime-kill assayTime-kill kineticsStudy evaluated <i>inMg/500 mgAmoxicillin-clavulanateTract infectionsSusceptibility testingQuantifying VMAT2 target occupancy at effective valbenazine doses and comparing to a novel VMAT2 inhibitor: a translational PET study
Terry-Lorenzo R, Albrecht D, Crouch S, Wong R, Loewen G, Giri N, Skor H, Lin K, Sandiego C, Pajonas M, Rabiner E, Gunn R, Russell D, Haubenberger D. Quantifying VMAT2 target occupancy at effective valbenazine doses and comparing to a novel VMAT2 inhibitor: a translational PET study. Neuropsychopharmacology 2025, 50: 1093-1101. PMID: 39757283, PMCID: PMC12089418, DOI: 10.1038/s41386-024-02046-3.Peer-Reviewed Original ResearchVesicular monoamine transporter type 2Treatment of tardive dyskinesiaPositron emission tomographyVesicular monoamine transporter type 2 inhibitorsTarget occupancyTreatment of chorea associated with Huntington's diseaseTreatment of TDChorea associated with Huntington's diseaseCentral nervous systemTardive dyskinesiaVMAT2 inhibitorsValbenazineClinical developmentEffect sizeAssociated with efficacyPET studiesEmission tomographyGold standard biomarkerDosing regimensClinical benefitDaily doseHuntington's diseaseActive metabolitePlasma concentrationsAcceptable dose
2024
Zinc finger nuclease-mediated gene editing in hematopoietic stem cells results in reactivation of fetal hemoglobin in sickle cell disease
Lessard S, Rimmelé P, Ling H, Moran K, Vieira B, Lin Y, Rajani G, Hong V, Reik A, Boismenu R, Hsu B, Chen M, Cockroft B, Uchida N, Tisdale J, Alavi A, Krishnamurti L, Abedi M, Galeon I, Reiner D, Wang L, Ramezi A, Rendo P, Walters M, Levasseur D, Peters R, Harris T, Hicks A. Zinc finger nuclease-mediated gene editing in hematopoietic stem cells results in reactivation of fetal hemoglobin in sickle cell disease. Scientific Reports 2024, 14: 24298. PMID: 39414860, PMCID: PMC11484757, DOI: 10.1038/s41598-024-74716-7.Peer-Reviewed Original ResearchConceptsHematopoietic stem cellsSickle cell diseaseTreatment of sickle cell diseaseFetal hemoglobinCell therapyReactivation of fetal hemoglobinCell diseaseMonths of follow-upStem cellsReactivate fetal hemoglobinResults of preclinical studiesPotential treatmentEngraftment in vivoAutologous cell therapyNovel cell therapiesVaso-occlusive crisisIncreased total hemoglobinErythroid progenyHealthy donorsPreclinical studiesClinical developmentFollow-upErythroid enhancerBCL11A erythroid enhancerGATAA motifsPARG inhibition induces nuclear aggregation of PARylated PARP1
Paradkar S, Purcell J, Cui A, Friedman S, Noronha K, Murray M, Sundaram R, Bindra R, Jensen R. PARG inhibition induces nuclear aggregation of PARylated PARP1. Structure 2024, 32: 2083-2093.e5. PMID: 39406247, DOI: 10.1016/j.str.2024.09.006.Peer-Reviewed Original ResearchSafety, tolerability, pharmacokinetics and pharmacodynamics of a single intravenous dose of SHR-1707 in healthy adult subjects: two randomized, double-blind, single-ascending-dose, phase 1 studies
Yang Y, Qiu H, Fan Y, Zhang Q, Qin H, Wu J, Zhang X, Liu Y, Zhou R, Zhang Q, Ye Z, Ma J, Xu Y, Feng S, Fei Y, Li N, Cui X, Dong F, Wang Q, Shen K, Shakib S, Williams J, Hu W. Safety, tolerability, pharmacokinetics and pharmacodynamics of a single intravenous dose of SHR-1707 in healthy adult subjects: two randomized, double-blind, single-ascending-dose, phase 1 studies. Alzheimer's Research & Therapy 2024, 16: 218. PMID: 39390616, PMCID: PMC11465679, DOI: 10.1186/s13195-024-01584-8.Peer-Reviewed Original ResearchConceptsTreatment-related adverse eventsPhase 1 studySingle-ascending-doseIntravenous doseHealthy adult subjectsDouble-blindElderly subjectsHealthy young adultsAdult subjectsTransient laboratory abnormalitiesPD profilesDose-proportional mannerSingle intravenous dosesYoung adultsDose-dependent increaseIgG1 monoclonal antibodyDose cohortsPlacebo groupLaboratory abnormalitiesPreclinical studiesAdverse eventsClinical developmentDose levelsNo ethnic differencesTransgenic miceTargeting APRIL in the treatment of glomerular diseases
Cheung C, Barratt J, Lafayette R, Liew A, Suzuki Y, Tesař V, Trimarchi H, Wong M, Zhang H, Rizk D. Targeting APRIL in the treatment of glomerular diseases. Kidney International 2024, 106: 806-818. PMID: 39182759, DOI: 10.1016/j.kint.2024.08.012.Peer-Reviewed Original ResearchGlomerular diseaseB cell depletion strategiesCytokine B cell-activating factorDeleterious host immune responsesFunctionality of humoral immunityMemory B-cell functionB-cell activating factorProliferation inducing ligandTreatment of glomerular diseasesB cell functionB cell developmentB cell survivalImmunoglobulin class switchingResponse to vaccinationClinical trial dataHost immune responseTumour necrosis factor (TNF)-superfamilyImmunomodulatory approachesAutoimmune diseasesClinical developmentInducing ligandIgA nephropathyHumoral immunityTherapeutic inhibitionClass switchingCT1812 biomarker signature from a meta‐analysis of CSF proteomic findings from two Phase 2 clinical trials in Alzheimer's disease
Lizama B, Williams C, North H, Pandey K, Duong D, Di V, Mecca A, Blennow K, Zetterberg H, Levey A, Grundman M, van Dyck C, Caggiano A, Seyfried N, Hamby M. CT1812 biomarker signature from a meta‐analysis of CSF proteomic findings from two Phase 2 clinical trials in Alzheimer's disease. Alzheimer's & Dementia 2024, 20: 6860-6880. PMID: 39166791, PMCID: PMC11485314, DOI: 10.1002/alz.14152.Peer-Reviewed Original ResearchVolumetric magnetic resonance imagingMagnetic resonance imagingPharmacodynamic biomarkersMeta-analysisClinical developmentCerebrospinal fluidPhase 2 clinical trialResonance imagingAlzheimer's diseaseMechanism of actionClinical trialsTandem mass tag-mass spectrometryClinical cohortMild to moderate ADCandidate biomarkersCT1812CohortBiomarker signaturesBiomarkersProteomic findingsUnbiased analysisNetwork analysisAmyloid-betaSynaptic biologyBiological impactVolenrelaxin (LY3540378) increases renal plasma flow: a randomized Phase 1 trial
San Tham L, Heerspink H, Wang X, Verdino P, Saifan C, Benson E, Goldsmith P, Wang Z, Testani J, Haupt A, Sam F, Cherney D. Volenrelaxin (LY3540378) increases renal plasma flow: a randomized Phase 1 trial. Nephrology Dialysis Transplantation 2024, 40: 109-122. PMID: 38782726, PMCID: PMC11659974, DOI: 10.1093/ndt/gfae112.Peer-Reviewed Original ResearchMeasured glomerular filtration rateEffective renal plasma flowRenal plasma flowKidney perfusionIncreased renal plasma flowPlacebo-adjusted changeMultiple-ascending dosePhase 1 trialGlomerular filtration rateChronic heart failureChronic kidney diseaseDiastolic blood pressureRenal arteriolar resistanceExtended half-lifeCardiorenal functionDouble-blindPlacebo SCRelaxin proteinSC doseAdverse eventsMeasured GFRArteriolar resistanceClinical developmentHeart failureOrthostatic hypotensionLAG-3, TIM-3, and TIGIT: Distinct functions in immune regulation
Joller N, Anderson A, Kuchroo V. LAG-3, TIM-3, and TIGIT: Distinct functions in immune regulation. Immunity 2024, 57: 206-222. PMID: 38354701, PMCID: PMC10919259, DOI: 10.1016/j.immuni.2024.01.010.Peer-Reviewed Original ResearchConceptsLAG-3Tim-3Immune cellsRestraining T-cell responsesImmune checkpoint receptorsT cell responsesRegulation of immune cellsImmune cell typesApplication of therapyPotential tissue toxicityCheckpoint receptorsTissue toxicityT cellsClinical developmentImmune regulationTIGITCell responsesReceptorsCell typesClinicCellsTherapyAbstract B026: Detection and characterization of DDR reversion alterations in baseline tissue and plasma samples from patients enrolled in the TRESR and ATTACC Phase I clinical trials
Silverman I, Schonhoft J, Jain E, Ulanet D, Yang J, Kim I, Fei K, Lagow E, Yablonovitch A, Cecchini M, Rosen E, Lee E, Lheureux S, Yap T, Fontana E, Koehler M, Rimkunas V. Abstract B026: Detection and characterization of DDR reversion alterations in baseline tissue and plasma samples from patients enrolled in the TRESR and ATTACC Phase I clinical trials. Cancer Research 2024, 84: b026-b026. DOI: 10.1158/1538-7445.dnarepair24-b026.Peer-Reviewed Original ResearchPoly(ADP-ribose) polymerase inhibitorsPhase I clinical trialDNA damage repairReversible alterationsECOG PS 0-1Baseline tissuePlatinum-based therapyPlasma samplesInterpretation of efficacy dataHRD-related genesDamage repairDDR alterationsTumor biopsiesOvarian cancerSingle nucleotide variantsWhole-genome sequencingDiagnostic challengeSolid tumorsClinical developmentEvaluate safetyEfficacy dataPolymerase inhibitorsTumorAtaxia telangiectasiaPatients
2023
Safety, tolerability, pharmacokinetics and pharmacodynamics of a single intravenous dose of SHR‐1707 in healthy adult subjects: two randomized, double‐blind, phase 1 studies
Hu W, Shakib S, Williams J, Fan Y, Zhang Q, Qin H, Wu J, Zhang X, Liu Y, Zhou R, Yang Y, Zhang Q, Ye Z, Qiu H, Ma J, Zhu M, Feng S, Fei Y, Li N, Cui X, Dong F, Wang T. Safety, tolerability, pharmacokinetics and pharmacodynamics of a single intravenous dose of SHR‐1707 in healthy adult subjects: two randomized, double‐blind, phase 1 studies. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.074758.Peer-Reviewed Original ResearchPhase 1 studySingle intravenous doseHealthy young adultsPK/PD profilesHealthy adult subjectsIntravenous doseElderly subjectsYoung adultsDose levelsPD profilesAdult subjectsDose-proportional mannerPK/pharmacodynamicsFurther clinical developmentDose-dependent increaseSame dose levelIgG1 monoclonal antibodyPlacebo groupLaboratory abnormalitiesMicroglial phagocytosisAβ plaquesPreclinical studiesSHRClinical developmentAβ42 concentrationsSafety, pharmacokinetics and pharmacodynamics of HRS‐7535, a novel oral small molecule glucagon‐like peptide‐1 receptor agonist, in healthy participants: A phase 1, randomized, double‐blind, placebo‐controlled, single‐ and multiple‐ascending dose, and food effect trial
Wu J, Zhou R, Zhang Q, Zhang Q, Qin H, Ye Z, Xu Y, Feng S, Shu C, Shen Y, Fan Y, Wang Q, Du Y, Hu W. Safety, pharmacokinetics and pharmacodynamics of HRS‐7535, a novel oral small molecule glucagon‐like peptide‐1 receptor agonist, in healthy participants: A phase 1, randomized, double‐blind, placebo‐controlled, single‐ and multiple‐ascending dose, and food effect trial. Diabetes Obesity And Metabolism 2023, 26: 901-910. PMID: 38100147, DOI: 10.1111/dom.15383.Peer-Reviewed Original ResearchGlucagon-like peptide-1 receptor agonistsPeptide-1 receptor agonistsSingle ascending doseMAD partsReceptor agonistGeometric mean tNovel glucagon-like peptide-1 receptor agonistFood effectHealthy participantsMultiple ascending dosePhase 1 trialType 2 diabetesGLP-1RAsPrimary endpointSingle doseDay 29Day 28Mean reductionClinical developmentMean TBody weightPharmacokineticsPlaceboTolerabilityEffect trialCase Study #8: Alpha-Therapy with Radium-223 Dichloride for Metastatic Castration-Resistant Prostate Cancer
Pasquini L, Morris M. Case Study #8: Alpha-Therapy with Radium-223 Dichloride for Metastatic Castration-Resistant Prostate Cancer. 2023, 387-405. DOI: 10.1007/978-3-031-39005-0_19.Peer-Reviewed Original ResearchMetastatic castration-resistant prostate cancerCastration-resistant prostate cancerProstate cancerRadium-223Radiopharmaceutical therapyTreatment of metastatic castration-resistant prostate cancerMinimal bone marrow toxicityRadium-223 dichlorideVisceral metastatic diseaseBone marrow toxicityNearby cancer cellsBone painMarrow toxicityMetastatic diseaseOverall survivalCombination therapyMetastatic spreadBone involvementAlpha therapyClinical developmentTreatment strategiesPalliative effectCancer cellsCancerBoneTheMarker: a comprehensive database of therapeutic biomarkers
Zhang Y, Zhou Y, Zhou Y, Yu X, Shen X, Hong Y, Zhang Y, Wang S, Mou M, Zhang J, Tao L, Gao J, Qiu Y, Chen Y, Zhu F. TheMarker: a comprehensive database of therapeutic biomarkers. Nucleic Acids Research 2023, 52: d1450-d1464. PMID: 37850638, PMCID: PMC10767989, DOI: 10.1093/nar/gkad862.Peer-Reviewed Original ResearchConceptsClinical practiceTherapeutic biomarkersTherapy-induced toxicityClinical outcomesPredictive biomarkersPharmacodynamic biomarkersClinical managementPrognostic biomarkerSafety biomarkersClinical developmentPatient statusPharmacological effectsMonitoring biomarkerTherapyBiomarkersAnticancer therapyDrug developmentDrug discoveryDisease classesStatusDatabaseClinical and research updates on the VISTA immune checkpoint: immuno-oncology themes and highlights
Noelle R, Lines J, Lewis L, Martell R, Guillaudeux T, Lee S, Mahoney K, Vesely M, Boyd-Kirkup J, Nambiar D, Scott A. Clinical and research updates on the VISTA immune checkpoint: immuno-oncology themes and highlights. Frontiers In Oncology 2023, 13: 1225081. PMID: 37795437, PMCID: PMC10547146, DOI: 10.3389/fonc.2023.1225081.Commentaries, Editorials and LettersImmune checkpoint proteinsImmune checkpointsImmune systemT-lymphocyte antigen-4Cell death protein 1V-domain immunoglobulin suppressorDeath protein 1CD28 family membersAnti-VISTA antibodyT cell activationImportant homeostatic functionsVISTA blockadePD-1Proinflammatory changesImmune effectsMyeloid suppressionAntigen-4CTLA-4Immune cellsT cellsImmune responsePreclinical studiesClinical developmentHomeostatic functionsMyeloid lineageTargeting a xenobiotic transporter to ameliorate vincristine-induced sensory neuropathy
Li Y, Drabison T, Nepal M, Ho R, Leblanc A, Gibson A, Jin Y, Yang W, Huang K, Uddin M, Chen M, DiGiacomo D, Chen X, Razzaq S, Tonniges J, McTigue D, Mims A, Lustberg M, Wang Y, Hummon A, Evans W, Baker S, Cavaletti G, Sparreboom A, Hu S. Targeting a xenobiotic transporter to ameliorate vincristine-induced sensory neuropathy. JCI Insight 2023, 8: e164646. PMID: 37347545, PMCID: PMC10443802, DOI: 10.1172/jci.insight.164646.Peer-Reviewed Original ResearchConceptsPeripheral neurotoxicitySide effectsDose-limiting peripheral neurotoxicityDorsal root ganglion neuronsMultiple malignant diseasesUptake of vincristineAction potential amplitudeEffective preventative treatmentMechanical allodyniaThermal hyperalgesiaSensory neuropathyGanglion neuronsMalignant diseasePlasma levelsDose selectionVincristine accumulationUntargeted metabolomics analysisAntitumor effectsClinical developmentPotential amplitudePreventative treatmentNeuronal transporterNeuronal morphologyVincristinePharmacological inhibitionOral therapy for myelodysplastic syndromes/neoplasms and acute myeloid leukemia: a revolution in progress
Venugopal S, Shallis R, Zeidan A. Oral therapy for myelodysplastic syndromes/neoplasms and acute myeloid leukemia: a revolution in progress. Expert Review Of Anticancer Therapy 2023, 23: 903-911. PMID: 37470508, DOI: 10.1080/14737140.2023.2238897.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAcute myeloid leukemiaOral therapyMyeloid leukemiaAllogeneic hematopoietic stem cell transplantationHematopoietic stem cell transplantationDisease-related complicationsDisease-directed therapyStem cell transplantationQuality of lifeCC-486HR-MDSOral azacitidineClinic visitsMost patientsGood tolerabilityIntensive therapyOptimal regimensCell transplantationTherapy combinationsTreatment optionsMedication administrationPatient outcomesMyeloid neoplasmsClinical developmentMyeloid malignanciesImmunobiology and Metabolic Pathways of Renal Cell Carcinoma
Braun D, Chakraborty A. Immunobiology and Metabolic Pathways of Renal Cell Carcinoma. Hematology/Oncology Clinics Of North America 2023, 37: 827-840. PMID: 37246090, DOI: 10.1016/j.hoc.2023.04.012.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsRenal cell carcinomaCell carcinomaAdvanced renal cell carcinomaClear cell renal cell carcinomaImmune checkpoint inhibitorsCell renal cell carcinomaNew treatment targetsFuture clinical developmentCheckpoint inhibitorsNovel therapeutic developmentDurable responsesMost patientsMetabolic dysregulationDistinct tumorsClinical developmentImmune pathwaysTreatment targetsTherapeutic developmentCarcinomaCurrent understandingMetabolic pathwaysPatientsImmunobiologyTumorsPathway
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