2025
Phase Ib study of PRT543, an oral protein arginine methyltransferase 5 (PRMT5) inhibitor, in patients with advanced splicing factor-mutant myeloid malignancies
Bewersdorf J, Mi X, Lu B, Kuykendall A, Sallman D, Patel M, Stevens D, Philipovskiy A, Sutamtewagul G, Masarova L, Keiffer G, Verma A, Bhagwat N, Wang M, Moore A, Rager J, Heiser D, Ro S, Hong W, Abdel-Wahab O, Stein E. Phase Ib study of PRT543, an oral protein arginine methyltransferase 5 (PRMT5) inhibitor, in patients with advanced splicing factor-mutant myeloid malignancies. Leukemia 2025, 39: 765-769. PMID: 39856223, PMCID: PMC11879867, DOI: 10.1038/s41375-025-02515-8.Peer-Reviewed Original ResearchProtein arginine methyltransferase 5Phase Ib studyMyeloid malignanciesArginine methyltransferase 5MalignancyPatients
2024
Phase Ib Study of PRT543, an Oral Protein Arginine Methyltransferase 5 (PRMT5) Inhibitor, in Patients with Relapsed or Refractory, Splicing Factor-Mutant Myeloid Malignancies
Bewersdorf J, Mi X, Lu B, Kuykendall A, Sallman D, Patel M, Stevens D, Philipovskiy A, Sutamtewagul G, Masarova L, Keiffer G, Verma A, Bhagwat N, Heiser D, Ro S, Hong W, Abdel-Wahab O, Stein E. Phase Ib Study of PRT543, an Oral Protein Arginine Methyltransferase 5 (PRMT5) Inhibitor, in Patients with Relapsed or Refractory, Splicing Factor-Mutant Myeloid Malignancies. Blood 2024, 144: 3215. DOI: 10.1182/blood-2024-198495.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsPlatelet transfusion independenceProtein arginine methyltransferase 5Myeloid malignanciesSplicing factor mutationsSymmetric dimethyl arginineMedian PFSTransfusion independenceFollow-upOpen-label phase Ib studyRed blood cell transfusion-dependentPRMT5 inhibitionAdequate end-organ functionBaseline serum EPO levelsRecommended phase 2 doseMedian duration of treatmentGrade 5 eventsLower-risk MDSMDS/MPN overlap syndromesPhase 2 doseIntensive induction chemotherapyPeripheral blood mononuclear cellsHigh-risk MDSPhase Ib studyMedian Follow-Up
2021
Acquired resistance to PRMT5 inhibition induces concomitant collateral sensitivity to paclitaxel
Mueller H, Fowler C, Dalin S, Moiso E, Udomlumleart T, Garg S, Hemann M, Lees J. Acquired resistance to PRMT5 inhibition induces concomitant collateral sensitivity to paclitaxel. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2024055118. PMID: 34408017, PMCID: PMC8403834, DOI: 10.1073/pnas.2024055118.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinoma of LungAnimalsAntineoplastic AgentsCell Line, TumorCell ProliferationDrug Resistance, NeoplasmDrug SynergismEpigenesis, GeneticGene Expression Regulation, NeoplasticGene Knockdown TechniquesHumansLung NeoplasmsMiceMutationPaclitaxelProtein-Arginine N-MethyltransferasesStathminConceptsProtein arginine methyltransferase 5Stathmin-2Sensitivity to paclitaxelPRMT5 inhibitorsLung adenocarcinomaPRMT5 inhibitionResponse to taxane treatmentCell linesArginine methyltransferase 5Resistance to inhibitorsRegression of tumorsMicrotubule regulationLung adenocarcinoma lineAcquisition of resistanceCancer cell linesPotential clinical relevanceEpigenetic regulationHuman cancer cell linesBarcoding experimentsMechanisms of resistanceTaxane treatmentPreexisting populationTaxanes paclitaxelCollateral sensitivityLung adenocarcinoma cells
2017
SHARPIN-mediated regulation of protein arginine methyltransferase 5 controls melanoma growth
Tamiya H, Kim H, Klymenko O, Kim H, Feng Y, Zhang T, Han JY, Murao A, Snipas SJ, Jilaveanu L, Brown K, Kluger H, Zhang H, Iwai K, Ronai Z. SHARPIN-mediated regulation of protein arginine methyltransferase 5 controls melanoma growth. Journal Of Clinical Investigation 2017, 128: 517-530. PMID: 29227283, PMCID: PMC5749505, DOI: 10.1172/jci95410.Peer-Reviewed Original ResearchConceptsLinear ubiquitin chain assembly complexType II protein arginine methyltransferaseProtein arginine methyltransferase 5Protein arginine methyltransferaseTranscription factor Sox10Cyclin-dependent kinase inhibitor 2ATranscriptional corepressor SKIArginine dimethylationArginine methyltransferasePRMT5 activityAssembly complexMelanoma growthMethyltransferase activityPRMT5PRMT5 inhibitionRegulatory axisInhibitor 2ASHARPINNF-κB signalingHuman cancersMethylthioadenosine phosphorylaseMultiproteinImportant roleDimethylationMethyltransferase
2016
MTAP deletion confers enhanced dependency on the PRMT5 arginine methyltransferase in cancer cells
Kryukov GV, Wilson FH, Ruth JR, Paulk J, Tsherniak A, Marlow SE, Vazquez F, Weir BA, Fitzgerald ME, Tanaka M, Bielski CM, Scott JM, Dennis C, Cowley GS, Boehm JS, Root DE, Golub TR, Clish CB, Bradner JE, Hahn WC, Garraway LA. MTAP deletion confers enhanced dependency on the PRMT5 arginine methyltransferase in cancer cells. Science 2016, 351: 1214-1218. PMID: 26912360, PMCID: PMC4997612, DOI: 10.1126/science.aad5214.Peer-Reviewed Original ResearchConceptsProtein arginine methyltransferase 5Methylthioadenosine phosphorylaseCancer cell linesMultiple cancer lineagesPutative drug targetsCell linesTumor suppressor geneComprehensive genomic profilingCancer cell dependenciesEnzyme methylthioadenosine phosphorylaseArginine methyltransferaseCancer lineagesFunctional characterizationCancer dependenciesPRMT5 inhibitorsSuppressor geneDrug targetsTherapeutic strategiesPreferential impairmentMTAP deletionEnzymatic activityGenomic alterationsGenomic profilingCell dependencyCancer cells
2008
Deciphering the assembly pathway of Sm‐class U snRNPs
Neuenkirchen N, Chari A, Fischer U. Deciphering the assembly pathway of Sm‐class U snRNPs. FEBS Letters 2008, 582: 1997-2003. PMID: 18348870, DOI: 10.1016/j.febslet.2008.03.009.Peer-Reviewed Original ResearchConceptsU snRNPsAssembly pathwayUridine-rich small nuclear ribonucleoproteinsProtein arginine methyltransferase 5SMN complex functionTrans-acting factorsSmall nuclear ribonucleoproteinNuclear ribonucleoproteinCommon proteinsSurvival motor neuronSm classSnRNPsProteinPathwayMotor neuronsRibonucleoproteinRecent progressRNASMNAssemblyLarge numberVitroVivoComplexes
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