2025
BCL2 inhibition for multiple myeloma and AL amyloidosis
Cani L, Gupta V, Kaufman J. BCL2 inhibition for multiple myeloma and AL amyloidosis. British Journal Of Haematology 2025 PMID: 40090369, DOI: 10.1111/bjh.20046.Peer-Reviewed Original ResearchMultiple myelomaAL amyloidosisBCL2 inhibitorsLight-chain (ALTreatment landscape of MMPlasma cell disorderMalignant blood disordersDevelopment of novel treatmentsBCL2 inhibitionTreatment landscapeDose optimizationCell disordersPatient selectionClinical studiesBlood disordersNovel treatmentAmyloidosisBCL2Light chainMyelomaToxicity concernsPatientsInhibitorsDrugTreatmentIn Vitro Inhibition of Voltage-Dependent Sodium Currents by the Antifungal Drug Amorolfine
Ghovanloo M, Tyagi S, Effraim P, Waxman S. In Vitro Inhibition of Voltage-Dependent Sodium Currents by the Antifungal Drug Amorolfine. Journal Of Biological Chemistry 2025, 108407. PMID: 40090585, DOI: 10.1016/j.jbc.2025.108407.Peer-Reviewed Original ResearchNav channelsInhibition of voltage-dependent sodium currentsLocal anestheticsVoltage-dependent sodium currentsStabilization of inactivationVoltage-gated sodiumSodium currentChannel inactivationChannel inhibitorsAmorolfineInactivated statePharmacological modulationIn vitro inhibitionIon channelsInhibitorsNavSelinexor plus ruxolitinib in JAK inhibitor treatment-naïve myelofibrosis: SENTRY Phase 3 study design
Mascarenhas J, Maher K, Rampal R, Bose P, Podoltsev N, Hong J, Chai Y, Kye S, Method M, Harrison C, . Selinexor plus ruxolitinib in JAK inhibitor treatment-naïve myelofibrosis: SENTRY Phase 3 study design. Future Oncology 2025, 21: 807-813. PMID: 39911057, PMCID: PMC11916360, DOI: 10.1080/14796694.2025.2461393.Peer-Reviewed Original ResearchConceptsJAK inhibitorsNo dose limiting toxicitiesDose-limiting toxicityAbsolute mean changeSpleen volume reductionPlacebo-controlled studyBaseline to weekTreatment of patientsDose expansionDose escalationLimiting toxicitiesDouble-blindPrimary endpointPhase 3 study designXPO1 inhibitorsMean changeRuxolitinibPatientsSelinexorVolume reductionDosePhase 3InhibitorsJAKMyelofibrosisExploring 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 approachPatients
2024
Immunogenicity of cell death and cancer immunotherapy with immune checkpoint inhibitors
Catanzaro E, Beltrán-Visiedo M, Galluzzi L, Krysko D. Immunogenicity of cell death and cancer immunotherapy with immune checkpoint inhibitors. Cellular & Molecular Immunology 2024, 22: 24-39. PMID: 39653769, PMCID: PMC11685666, DOI: 10.1038/s41423-024-01245-8.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsImmunogenic cell deathImmunogenic cell death inducerCheckpoint inhibitorsRefractory to immune checkpoint inhibitorsImmunogenicity of cell deathFraction of patientsCombinatorial treatment strategiesAdaptive immune responsesCell deathCombinatorial partnersCancer immunotherapyCombinatorial regimensClinical findingsClinical managementTreatment strategiesClinical activityImmune responseImmunotherapyPatientsCancerOncology settingInhibitorsDeathInducerElectron tomography visualization of HIV-1 virions trapped by fusion inhibitors to host cells in infected tissues
Ladinsky M, Zhu L, Ullah I, Uchil P, Kumar P, Kay M, Bjorkman P. Electron tomography visualization of HIV-1 virions trapped by fusion inhibitors to host cells in infected tissues. Journal Of Virology 2024, 98: e01432-24. PMID: 39475277, PMCID: PMC11575291, DOI: 10.1128/jvi.01432-24.Peer-Reviewed Original ResearchHIV-1 virionsHIV-1 target cellsHIV-1Fusion inhibitorsTarget cellsBone marrow/liver/thymus miceHIV-1 pseudovirionsCo-receptorHost cell membraneTZM-bl cellsPre-hairpin intermediateVascular endothelial cellsCell surfaceHumanized miceTZM-blCell membraneInfected tissuesEnvEndothelial cellsViral envelopeBind host receptorsHost receptorsInhibitorsCo-receptor proteinsPresence of virionsElectroencephalography (EEG) spectral signatures of selective serotonin reuptake inhibitors (SSRIs), selective norepinephrine reuptake inhibitors (SNRIs) and vortioxetine in major depressive disorder: A systematic review
Le G, Wong S, Lu A, Vasudeva S, Gill H, Badulescu S, Portelles D, Zheng Y, Teopiz K, Meshkat S, Kwan A, Ho R, Rhee T, Rosenblat J, Mansur R, McIntyre R. Electroencephalography (EEG) spectral signatures of selective serotonin reuptake inhibitors (SSRIs), selective norepinephrine reuptake inhibitors (SNRIs) and vortioxetine in major depressive disorder: A systematic review. Journal Of Affective Disorders 2024, 368: 798-819. PMID: 39299586, DOI: 10.1016/j.jad.2024.09.081.Peer-Reviewed Original ResearchReuptake inhibitorsDepressive disorderPathophysiology of depressive disordersSystematic reviewAssociated with SSRIsClass of SSRIsNorepinephrine reuptake inhibitorsDoses of antidepressantsSerotonin reuptake inhibitorsFDA-approved agentsVortioxetine treatmentBlock reuptakeAntidepressant exposureSerotonin transporterSNRISSRIsVortioxetineDatabase inceptionConverging evidenceFunctional connectivitySerotoninNeural activityElectroencephalography signaturesStudy investigated changesInhibitorsState-of-the-Art Advancements in Gastroesophageal Cancer Treatment: Harnessing Biomarkers for Precision Care.
Balmaceda N, Petrillo A, Krishnan M, Zhao J, Kim S, Klute K, Sundar R. State-of-the-Art Advancements in Gastroesophageal Cancer Treatment: Harnessing Biomarkers for Precision Care. American Society Of Clinical Oncology Educational Book 2024, 44: e431060. PMID: 38771996, DOI: 10.1200/edbk_431060.Peer-Reviewed Original ResearchConceptsGastroesophageal cancerIntegration of immune checkpoint inhibitorsChimeric antigen receptor T cellsImmune checkpoint inhibitorsMetastatic gastroesophageal cancerPD-1 inhibitorsAdoptive cell therapyImmunotherapy-based approachesResectable gastroesophageal cancerAntibody-drug conjugatesCheckpoint inhibitorsPD-1Perioperative chemotherapyTargeted therapyT cellsTreatment paradigmFGFR2 inhibitorsCell therapyClinical challengeBispecific antibodiesImprove outcomesCancer treatmentReduced toxicityTherapyInhibitorsNavigating practical challenges in immunotherapy for metastatic triple negative breast cancer
Licata L, Dieci M, De Angelis C, Marchiò C, Miglietta F, Cortesi L, Fabi A, Schmid P, Cortes J, Pusztai L, Bianchini G, Curigliano G. Navigating practical challenges in immunotherapy for metastatic triple negative breast cancer. Cancer Treatment Reviews 2024, 128: 102762. PMID: 38776613, DOI: 10.1016/j.ctrv.2024.102762.Peer-Reviewed Original ResearchTriple-negative breast cancerBreast cancerMetastatic triple negative breast cancerManagement of breast cancer patientsTriple negative breast cancerApproval of immunotherapyImmune checkpoint inhibitorsNegative breast cancerBreast cancer patientsEveryday clinical practiceCheckpoint inhibitorsTumor typesCancer patientsClinical trialsCancer therapyImmunotherapyCancerClinical practicePositive resultsCliniciansTumorTherapyPatientsTrialsInhibitorsCrystallographic 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
ALK inhibitors increase ALK expression and sensitize neuroblastoma cells to ALK.CAR-T cells
Bergaggio E, Tai W, Aroldi A, Mecca C, Landoni E, Nüesch M, Mota I, Metovic J, Molinaro L, Ma L, Alvarado D, Ambrogio C, Voena C, Blasco R, Li T, Klein D, Irvine D, Papotti M, Savoldo B, Dotti G, Chiarle R. ALK inhibitors increase ALK expression and sensitize neuroblastoma cells to ALK.CAR-T cells. Cancer Cell 2023, 41: 2100-2116.e10. PMID: 38039964, PMCID: PMC10793157, DOI: 10.1016/j.ccell.2023.11.004.Peer-Reviewed Original ResearchConceptsALK inhibitorsALK expressionChimeric antigen receptor TBest tumor antigensPromising clinical activityExpression of ALKMost normal tissuesHematologic malignanciesClinical activityMost neuroblastomasAnaplastic lymphoma kinase (ALK) receptorTherapeutic successTumor antigensPotent efficacySolid tumorsTherapeutic efficacyNeuroblastomaTumor growthOncogenic driversNeuroblastoma cellsNormal tissuesALKKinase receptorsMonotherapyInhibitorsExploring 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, 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 propertiesBrainCovalent and noncovalent strategies for targeting Lys102 in HIV-1 reverse transcriptase
Prucha G, Henry S, Hollander K, Carter Z, Spasov K, Jorgensen W, Anderson K. Covalent and noncovalent strategies for targeting Lys102 in HIV-1 reverse transcriptase. European Journal Of Medicinal Chemistry 2023, 262: 115894. PMID: 37883896, PMCID: PMC10872499, DOI: 10.1016/j.ejmech.2023.115894.Peer-Reviewed Original ResearchInhibition of a lower potency target drives the anticancer activity of a clinical p38 inhibitor
Bhattacharjee D, Bakar J, Chitnis S, Sausville E, Ashtekar K, Mendelson B, Long K, Smith J, Heppner D, Sheltzer J. Inhibition of a lower potency target drives the anticancer activity of a clinical p38 inhibitor. Cell Chemical Biology 2023, 30: 1211-1222.e5. PMID: 37827156, PMCID: PMC10715717, DOI: 10.1016/j.chembiol.2023.09.013.Peer-Reviewed Original ResearchPI3Kδ Pathway Dysregulation and Unique Features of Its Inhibition by Leniolisib in Activated PI3Kδ Syndrome and Beyond
Cant A, Chandra A, Munro E, Rao V, Lucas C. PI3Kδ Pathway Dysregulation and Unique Features of Its Inhibition by Leniolisib in Activated PI3Kδ Syndrome and Beyond. The Journal Of Allergy And Clinical Immunology In Practice 2023, 12: 69-78. PMID: 37777067, PMCID: PMC10872751, DOI: 10.1016/j.jaip.2023.09.016.Peer-Reviewed Original ResearchConceptsPI3Kδ inhibitorsActivated PI3Kδ SyndromeImmune cell developmentPI3Kδ syndromeSpecific inhibitory propertiesAdverse eventsTreatment optionsPI3Kδ activityHematological malignanciesPathway dysregulationInborn errorsDrug mechanismsGenetic hyperactivationLeniolisibSyndromeΔ isoformsCell developmentInhibitorsInhibitory propertiesΓ isoformsColitisNeutropeniaTolerabilityMalignancyHepatotoxicityEnhancing HCC Treatment: innovatively combining HDAC2 inhibitor with PD-1/PD-L1 inhibition
Han R, Ling C, Wang Y, Lu L. Enhancing HCC Treatment: innovatively combining HDAC2 inhibitor with PD-1/PD-L1 inhibition. Cancer Cell International 2023, 23: 203. PMID: 37716965, PMCID: PMC10504701, DOI: 10.1186/s12935-023-03051-0.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsHepatocellular carcinomaCheckpoint inhibitorsHCC treatmentPD-1/PD-L1 inhibitionPD-1/PD-L1 inhibitorsHDAC2 inhibitorsTreatment of HCCPD-L1 inhibitionAnti-cancer immunityPD-L1 inhibitorsAnti-tumor efficacyNew combination strategiesPD-L1Clinical benefitHigh morbidityTherapeutic effectSolid cancersEffective treatmentLatest evidenceNuclear translocationTreatmentInhibitorsCombination strategiesEfficacyCardiothoracic complications of immune checkpoint inhibitors
Gosangi B, Wang Y, Rubinowitz A, Kwan J, Traube L, Gange C, Bader A. Cardiothoracic complications of immune checkpoint inhibitors. Clinical Imaging 2023, 102: 98-108. PMID: 37659356, DOI: 10.1016/j.clinimag.2023.08.001.Peer-Reviewed Educational MaterialsConceptsImmune checkpoint inhibitorsICI therapyCheckpoint inhibitorsOverall survivalTumor responseAdverse effectsDevelopment of irAEsNovel adverse effectsImproved overall survivalOverall patient outcomesICI administrationHematologic malignanciesPatient outcomesSolid tumorsIrAEsCancer treatmentGreater mortalityComplicationsTherapySurvivalInhibitorsMyocarditisPneumonitisPatientsMalignancySociety for Immunotherapy of Cancer (SITC) checkpoint inhibitor resistance definitions: efforts to harmonize terminology and accelerate immuno-oncology drug development
Tawbi H, Sullivan R, Feltquate D, LaVallee T, Rizvi N, Sharon E, Sosman J, Kluger H. Society for Immunotherapy of Cancer (SITC) checkpoint inhibitor resistance definitions: efforts to harmonize terminology and accelerate immuno-oncology drug development. Journal For ImmunoTherapy Of Cancer 2023, 11: e007309. PMID: 37487665, PMCID: PMC10373737, DOI: 10.1136/jitc-2023-007309.Peer-Reviewed Original ResearchTackling FGFR3-driven bladder cancer with a promising synergistic FGFR/HDAC targeted therapy
Wang Z, Muthusamy V, Petrylak D, Anderson K. Tackling FGFR3-driven bladder cancer with a promising synergistic FGFR/HDAC targeted therapy. Npj Precision Oncology 2023, 7: 70. PMID: 37479885, PMCID: PMC10362036, DOI: 10.1038/s41698-023-00417-5.Peer-Reviewed Original ResearchBladder cancerBC cellsEarly phase clinical trialsPhase clinical trialsDurable responsesMetastatic diseaseMost patientsFGFR3 alterationsPrevalent malignancyClinical trialsFGFR3 fusionsPreclinical studiesFGFR inhibitorsHDAC inhibitorsFGFR3 expressionEfficient therapyTherapyCancerQuisinostatFGFR3New mechanistic insightsInhibitorsCellsPatientsMalignancy
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