2021
Brain target occupancy of LY3372689, an inhibitor of the O‐GlcNAcase (OGA) enzyme, following administration of single and multiple doses to healthy volunteers
Kielbasa W, Shcherbinin S, Goldsmith P, Phipps K, Biglan K, Mancini M, Russell D, Constantinescu C, Gunn R, Nuthall H, Mergott D, Lowe S, Collins E. Brain target occupancy of LY3372689, an inhibitor of the O‐GlcNAcase (OGA) enzyme, following administration of single and multiple doses to healthy volunteers. Alzheimer's & Dementia 2021, 17 DOI: 10.1002/alz.057774.Peer-Reviewed Original ResearchHealthy volunteersEnzyme occupancyPET scansSingle doseMultiple-dose clinical studiesPost-dose intervalPositron emission tomography radioligandBaseline PET scanLonger clinical trialsTarget occupancyTau-related diseasesMultiple dosesMultiple dosingClinical trialsPlasma pharmacokineticsClinical studiesEfficacy trialsSD studiesDose selectionTomography radioligandEnzyme inhibitorsPotential treatmentAlzheimer's diseasePET studiesTarget engagement
2020
Brain target occupancy of LY3372689, an inhibitor of the O‐GlcNAcase (OGA) enzyme: Translation from rat to human
Shcherbinin S, Kielbasa W, Dubois S, Lowe S, Phipps K, Tseng J, Kevin D, Natanegara F, Warner S, Dreyfus N, Lindsay‐Scott P, Hawk M, McDonald N, Zhang X, Gilmore J, Biglan K, Mergott D, Russell D, Gunn R, Constantinescu C, Nuthall H, Collins E. Brain target occupancy of LY3372689, an inhibitor of the O‐GlcNAcase (OGA) enzyme: Translation from rat to human. Alzheimer's & Dementia 2020, 16 DOI: 10.1002/alz.040558.Peer-Reviewed Original ResearchPET scansEnzyme occupancyHealthy volunteersPlasma concentration-dependent increaseSingle oral dose studyOral dose studyBaseline PET scanSingle oral doseTau-related diseasesDose-dependent changesConcentration-dependent increaseHuman PET studiesDose cohortsOral doseSingle dosesDose studyClinical studiesEfficacy trialsPharmacokinetic samplesFrontal cortexInitial cohortDose selectionHigh doseNumber of subjectsEnzyme inhibitors
2018
T156. IN VIVO CHARACTERIZATION OF THE FIRST AGONIST DOPAMINE D1 RECEPTORS PET IMAGING TRACER [18F]MNI-968 IN HUMAN
Tamagnan G, Barret O, Alagille D, Carroll V, Madonia J, Constantinescu C, SanDiego C, Papin C, Morley T, Russell D, McCarthy T, Zhang L, Gray D, Villalobos A, Lee C, Chen J, Seibyl J, Marek K. T156. IN VIVO CHARACTERIZATION OF THE FIRST AGONIST DOPAMINE D1 RECEPTORS PET IMAGING TRACER [18F]MNI-968 IN HUMAN. Schizophrenia Bulletin 2018, 44: s176-s176. PMCID: PMC5888516, DOI: 10.1093/schbul/sby016.432.Peer-Reviewed Original ResearchLogan graphical analysisNon-human primatesRhesus monkeysD1 receptorsBlockade studiesPET studiesPET radiotracersD1 receptor occupancyWhole-brain uptakeNovel PET radiotracersInhibitory G proteinSame dose levelMin post injectionHealthy human volunteersTest-retest reproducibilityBrain PET studiesPET imaging tracerAgonist PET tracerClinical studiesStriatal regionsInjected dosePsychiatric disordersCerebellar cortexDose levelsReceptor occupancy