2024
The HER2-directed antibody-drug conjugate DHES0815A in advanced and/or metastatic breast cancer: preclinical characterization and phase 1 trial results
Lewis G, Li G, Guo J, Yu S, Fields C, Lee G, Zhang D, Dragovich P, Pillow T, Wei B, Sadowsky J, Leipold D, Wilson T, Kamath A, Mamounas M, Lee M, Saad O, Choeurng V, Ungewickell A, Monemi S, Crocker L, Kalinsky K, Modi S, Jung K, Hamilton E, LoRusso P, Krop I, Schutten M, Commerford R, Sliwkowski M, Cho E. The HER2-directed antibody-drug conjugate DHES0815A in advanced and/or metastatic breast cancer: preclinical characterization and phase 1 trial results. Nature Communications 2024, 15: 466. PMID: 38212321, PMCID: PMC10784567, DOI: 10.1038/s41467-023-44533-z.Peer-Reviewed Original ResearchConceptsHER2 antibody-drug conjugatesAntibody-drug conjugatesMetastatic breast cancerPhase 1 trialBreast cancerHER2-positive metastatic breast cancerHER2-positive breast cancerObjective response rateDose-escalation studyDuration of responseModel of HER2Anti-tumor activityMechanism of actionTrastuzumab deruxtecanPulmonary toxicityTrastuzumab emtansinePreclinical characterizationResponse rateHigh dosesVivo efficacySecondary objectiveEarly signsPotent cytotoxic agentCytotoxic agentsCancer
2022
EP015/#546 In vitro and in vivo efficacy of trastuzumab deruxtecan (T-DXd) in epithelial ovarian cancer with HER2/NEU overexpression
Mutlu L, Manavella D, Bellone S, Santin A. EP015/#546 In vitro and in vivo efficacy of trastuzumab deruxtecan (T-DXd) in epithelial ovarian cancer with HER2/NEU overexpression. International Journal Of Gynecological Cancer 2022, 32: a54. DOI: 10.1136/ijgc-2022-igcs.106.Peer-Reviewed Original Research
2021
Mutant-selective degradation by BRAF-targeting PROTACs
Alabi S, Jaime-Figueroa S, Yao Z, Gao Y, Hines J, Samarasinghe KTG, Vogt L, Rosen N, Crews CM. Mutant-selective degradation by BRAF-targeting PROTACs. Nature Communications 2021, 12: 920. PMID: 33568647, PMCID: PMC7876048, DOI: 10.1038/s41467-021-21159-7.Peer-Reviewed Original ResearchConceptsInhibitor-based therapyBRAF inhibitor-based therapiesBRAF missense mutationsCancer cell growthBRAF V600Current treatmentNew therapiesTherapeutic windowXenograft modelBRAF mutantMutant BRAFVivo efficacyDrug modalitiesRaf family membersProteolysis targeting chimera (PROTAC) technologyTherapyBRAFMissense mutationsFamily membersBRAFWTCell growthDegree of selectivityInactivated conformationPatientsV600
2020
Monitoring Atsttrin-Mediated Inhibition of TNFα/NF-κβ Activation Through In Vivo Bioluminescence Imaging
Hettinghouse A, Fu W, Liu C. Monitoring Atsttrin-Mediated Inhibition of TNFα/NF-κβ Activation Through In Vivo Bioluminescence Imaging. Methods In Molecular Biology 2020, 2248: 201-210. PMID: 33185877, PMCID: PMC8140391, DOI: 10.1007/978-1-0716-1130-2_14.Peer-Reviewed Original ResearchConceptsTumor necrosis factorDouble mutant miceNF-κBOverexpression of TNFMutant miceBioluminescence imagingTransgenic reporter mouse modelNF-κB luciferaseNF-κβ activationVivo bioluminescence imagingReporter mouse modelAutoimmune conditionsTNF-TgNF-κβNecrosis factorImmune responseMouse modelMolecular mediatorsTransgenic modelTherapeutic objectivesVivo efficacyProgranulinPotential therapeuticsAtsttrinLuciferase activityIn vivo efficacy of bevacizumab-loaded albumin nanoparticles in the treatment of colorectal cancer
Luis de Redín I, Expósito F, Agüeros M, Collantes M, Peñuelas I, Allemandi D, Llabot JM, Calvo A, Irache JM. In vivo efficacy of bevacizumab-loaded albumin nanoparticles in the treatment of colorectal cancer. Drug Delivery And Translational Research 2020, 10: 635-645. PMID: 32040774, DOI: 10.1007/s13346-020-00722-7.Peer-Reviewed Original ResearchConceptsAlbumin nanoparticlesHuman serum albumin nanoparticlesAlbumin-based nanoparticlesSerum albumin nanoparticlesPoor tumor penetrationNanoparticlesColorectal cancerTumor penetrationFree bevacizumabXenograft modelAdequate carrierMean sizeHT-29 xenograft modelMetabolic tumor volumePotential undesirable side effectsHuman colorectal cancerTumor growth rateConventional formulationUndesirable side effectsLower incidenceTumor volumeBevacizumabEffective treatmentSide effectsVivo efficacy
2017
Targeting the vulnerability to NAD+ depletion in B-cell acute lymphoblastic leukemia
Takao S, Chien W, Madan V, Lin D, Ding L, Sun Q, Mayakonda A, Sudo M, Xu L, Chen Y, Jiang Y, Gery S, Lill M, Park E, Senapedis W, Baloglu E, Müschen M, Koeffler H. Targeting the vulnerability to NAD+ depletion in B-cell acute lymphoblastic leukemia. Leukemia 2017, 32: 616-625. PMID: 28904384, DOI: 10.1038/leu.2017.281.Peer-Reviewed Original ResearchMeSH KeywordsAcrylamidesAminopyridinesAnimalsAntineoplastic AgentsApoptosisCell Line, TumorCell ProliferationCell SurvivalCytokinesDisease Models, AnimalFemaleHumansMaleMiceNADNicotinamide Phosphoribosyltransferasep21-Activated KinasesPrecursor B-Cell Lymphoblastic Leukemia-LymphomaSignal TransductionXenograft Model Antitumor AssaysConceptsB-cell acute lymphoblastic leukemiaAcute lymphoblastic leukemiaP21-activated kinase 4Nicotinamide phosphoribosyltransferaseLymphoblastic leukemiaNAMPT inhibitionPatient-derived xenograft murine modelsPrognosis of patientsNicotinamide adenine dinucleotideNovel therapeutic strategiesNicotinic acid supplementationNovel dual inhibitorXenograft murine modelCell growth inhibitionAcid supplementationMurine modelTherapeutic strategiesRate-limiting enzymeCytogenetic abnormalitiesVivo efficacyPatientsNAMPT inhibitorsInhibitory effectDual inhibitorKinase 4
2016
ARV-330: Androgen receptor PROTAC degrader for prostate cancer.
Neklesa T, Jin M, Crew A, Rossi A, Willard R, Dong H, Siu K, Wang J, Gordon D, Chen X, Ferraro C, Crews C, Coleman K, Winkler J. ARV-330: Androgen receptor PROTAC degrader for prostate cancer. Journal Of Clinical Oncology 2016, 34: 267-267. DOI: 10.1200/jco.2016.34.2_suppl.267.Peer-Reviewed Original ResearchAndrogen receptorAR mutationsProstate cancerTotal androgen receptorTreatment of miceAR protein levelsProstate cancer cellsGood pharmacokinetic propertiesPlasma PSAMetastatic diseaseNM R1881SC injectionAndrogen productionDisease progressionPSA expressionIntact miceTherapeutic effectCastrated miceVCaP cellsAnimal modelsProstate involutionTumor growthVivo efficacyPreclinical developmentPharmacokinetic properties
2014
Systemic Delivery of Microencapsulated 3-Bromopyruvate for the Therapy of Pancreatic Cancer
Chapiro J, Sur S, Savic LJ, Ganapathy-Kanniappan S, Reyes J, Duran R, Thiruganasambandam SC, Moats CR, Lin M, Luo W, Tran PT, Herman JM, Semenza GL, Ewald AJ, Vogelstein B, Geschwind JF. Systemic Delivery of Microencapsulated 3-Bromopyruvate for the Therapy of Pancreatic Cancer. Clinical Cancer Research 2014, 20: 6406-6417. PMID: 25326230, PMCID: PMC4300523, DOI: 10.1158/1078-0432.ccr-14-1271.Peer-Reviewed Original ResearchConceptsPancreatic ductal adenocarcinomaSuit-2 cell lineOrthotopic xenograft mouse modelBioluminescence imagingFavorable toxicity profileSublethal drug concentrationsAnti-invasive effectsXenograft mouse modelPDAC cell linesCell linesXenograft tumor modelHalf maximal inhibitory concentrationStrong anticancer effectsPancreatic cancerClinical trialsDuctal adenocarcinomaMouse modelToxicity profileIC50 profileTherapeutic efficacyMatrigel invasionVivo efficacyBLI signalMatrigel assaysMiaPaCa-2Discovery of a New Class of Non-β-lactam Inhibitors of Penicillin-Binding Proteins with Gram-Positive Antibacterial Activity
O’Daniel P, Peng Z, Pi H, Testero S, Ding D, Spink E, Leemans E, Boudreau M, Yamaguchi T, Schroeder V, Wolter W, Llarrull L, Song W, Lastochkin E, Kumarasiri M, Antunes N, Espahbodi M, Lichtenwalter K, Suckow M, Vakulenko S, Mobashery S, Chang M. Discovery of a New Class of Non-β-lactam Inhibitors of Penicillin-Binding Proteins with Gram-Positive Antibacterial Activity. Journal Of The American Chemical Society 2014, 136: 3664-3672. PMID: 24517363, PMCID: PMC3985699, DOI: 10.1021/ja500053x.Peer-Reviewed Original ResearchConceptsMethicillin-resistant Staphylococcus aureusPenicillin-binding protein 2aLinezolid-resistant methicillin-resistant Staphylococcus aureusNon-β-lactam antibioticsGlobal public health concernSerious global public health concernPublic health concernClasses of antibioticsMouse modelVivo efficacyOral bioavailabilityProtein 2ABactericidal activityGram-positive antibacterial activityStaphylococcus aureusNon-β-lactam inhibitorsInfectionPenicillin binding proteinsAntibioticsAntibacterial activityVancomycin
2013
The nanomaterial-dependent modulation of dendritic cells and its potential influence on therapeutic immunosuppression in lupus
Look M, Saltzman WM, Craft J, Fahmy TM. The nanomaterial-dependent modulation of dendritic cells and its potential influence on therapeutic immunosuppression in lupus. Biomaterials 2013, 35: 1089-1095. PMID: 24183697, PMCID: PMC4164020, DOI: 10.1016/j.biomaterials.2013.10.046.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedDendritic CellsDrug CarriersFemaleImmunosuppression TherapyImmunosuppressive AgentsLactic AcidLupus Erythematosus, SystemicMiceMice, Inbred BALB CMice, Inbred C57BLMice, Inbred NZBMycophenolic AcidNanogelsPermeabilityPolyethylene GlycolsPolyethyleneiminePolyglycolic AcidPolylactic Acid-Polyglycolic Acid CopolymerConceptsDendritic cellsTherapeutic immunosuppressionLupus-prone NZB/W F1 miceNZB/W F1 miceW F1 miceCell immunosuppressionImmunosuppressive therapyInflammatory cytokinesImmune modulatorsF1 miceImmune responseImmunosuppressionVivo efficacySurface markersMycophenolic acidGreater reductionParticulate uptakeAttractive modalityEfficacyCellsNanoparticulate platformSuccessful deliveryImmunosuppressantsLupusCytokines
2010
In vitro and in vivo evaluation of a whole blood platelet‐sparing leukoreduction filtration system
Snyder EL, Whitley P, Kingsbury T, Miripol J, Tormey CA. In vitro and in vivo evaluation of a whole blood platelet‐sparing leukoreduction filtration system. Transfusion 2010, 50: 2145-2151. PMID: 20497514, DOI: 10.1111/j.1537-2995.2010.02701.x.Peer-Reviewed Original ResearchConceptsRed blood cellsWhite blood cellsAutologous plateletsTransfusion productsBlood cellsAdverse clinical sequelaeCPD plasmaProduction of plateletsResidual white blood cellsClinical sequelaeDrug Administration requirementsHospital useVivo efficacyLeukoreduction filtersBlood centersStudy designVivo evaluationLR productsVivo characteristicsPlateletsRBC recoveryAdministration requirementsVitroSurvival ratioFDA guidelines
2009
Discovery of 4-(5-Methyloxazolo[4,5-b]pyridin-2-yl)-1,4-diazabicyclo[3.2.2]nonane (CP-810,123), a Novel α7 Nicotinic Acetylcholine Receptor Agonist for the Treatment of Cognitive Disorders in Schizophrenia: Synthesis, SAR Development, and in Vivo Efficacy in Cognition Models
O’Donnell C, Rogers B, Bronk B, Bryce D, Coe J, Cook K, Duplantier A, Evrard E, Hajós M, Hoffmann W, Hurst R, Maklad N, Mather R, McLean S, Nedza F, O’Neill B, Peng L, Qian W, Rottas M, Sands S, Schmidt A, Shrikhande A, Spracklin D, Wong D, Zhang A, Zhang L. Discovery of 4-(5-Methyloxazolo[4,5-b]pyridin-2-yl)-1,4-diazabicyclo[3.2.2]nonane (CP-810,123), a Novel α7 Nicotinic Acetylcholine Receptor Agonist for the Treatment of Cognitive Disorders in Schizophrenia: Synthesis, SAR Development, and in Vivo Efficacy in Cognition Models. Journal Of Medicinal Chemistry 2009, 53: 1222-1237. PMID: 20043678, DOI: 10.1021/jm9015075.Peer-Reviewed Original ResearchMeSH Keywordsalpha7 Nicotinic Acetylcholine ReceptorAnimalsAzabicyclo CompoundsBiological AvailabilityCells, CulturedCognition DisordersEpithelial CellsFemaleHippocampusHumansKidneyMicrosomes, LiverNicotinic AgonistsNootropic AgentsOocytesOxazolesRatsReceptors, NicotinicSchizophreniaSkinStructure-Activity RelationshipXenopus laevisConceptsVivo efficacyΑ7 nicotinic acetylcholine receptor agonistCognitive deficitsAlpha 7Nicotinic acetylcholine receptor agonistExcellent brain penetrationAcetylcholine receptor agonistNovel object recognitionAuditory sensory gatingHigh oral bioavailabilityBrain penetrationReceptor agonistNeurological conditionsCognitive disordersPotential treatmentReceptor occupancySensory gatingAlzheimer's diseaseOral bioavailabilityAgonistsSchizophreniaTreatmentDiseaseCompound 24Efficacy
2001
NMR Spectroscopy in β Cell Engineering and Islet Transplantation
PAPAS K, COLTON C, GOUNARIDES J, ROOS E, JAREMA M, SHAPIRO M, CHENG L, CLINE G, SHULMAN G, WU H, BONNER‐WEIR S, WEIR G. NMR Spectroscopy in β Cell Engineering and Islet Transplantation. Annals Of The New York Academy Of Sciences 2001, 944: 96-119. PMID: 11797699, DOI: 10.1111/j.1749-6632.2001.tb03826.x.Peer-Reviewed Original ResearchConceptsIslet transplantationGlucose metabolismBeta cellsLong-term complicationsIrreversible damageTerm complicationsOxidative glucose metabolismAcute ischemiaTransplantationVivo efficacyHuman isletsIslet preparationsC-myc oncogeneSecreting tissueCell damageSuch exposureGenetic alterationsBcl-2Overnight incubationIslet transportationIslets
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