Exploring drug delivery for the DOT1L inhibitor pinometostat (EPZ-5676): Subcutaneous administration as an alternative to continuous IV infusion, in the pursuit of an epigenetic target
Waters NJ, Daigle SR, Rehlaender BN, Basavapathruni A, Campbell CT, Jensen TB, Truitt BF, Olhava EJ, Pollock RM, Stickland KA, Dovletoglou A. Exploring drug delivery for the DOT1L inhibitor pinometostat (EPZ-5676): Subcutaneous administration as an alternative to continuous IV infusion, in the pursuit of an epigenetic target. Journal Of Controlled Release 2015, 220: 758-765. PMID: 26385168, DOI: 10.1016/j.jconrel.2015.09.023.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAnimalsAntineoplastic AgentsBenzimidazolesBiological AvailabilityChemistry, PharmaceuticalDelayed-Action PreparationsDNA MethylationDogsDrug Administration ScheduleDrug CarriersEnzyme InhibitorsEpigenesis, GeneticGene Expression Regulation, LeukemicHistone-Lysine N-MethyltransferaseHumansInfusions, IntravenousInjections, SubcutaneousLeukemia, Biphenotypic, AcuteMaleMethyltransferasesMiceRats, Sprague-DawleyTumor BurdenXenograft Model Antitumor AssaysConceptsXenograft modelRefractory acute leukemia patientsFurther evaluationPhase 1 clinical trialSubcutaneous bolus administrationAcute leukemia patientsTumor growth inhibitionDOT1L inhibitor pinometostatExtended-release formulationRat xenograft modelMLL-r leukemiaThrice dailyPharmacodynamic markersSC administrationBolus administrationClinical trialsSubcutaneous administrationComplete bioavailabilityDOT1L activityLeukemia patientsOral administrationPatient conveniencePreclinical studiesSmall molecule inhibitorsImproved exposure