2019
Effective Novel Fto Inhibitors Show Potent Anti-Cancer Efficacy and Suppress Drug Resistance
Su R, Dong L, Li Y, Han L, Gao M, Wunderlich M, Deng X, Li H, Gao L, Li C, Robison S, Tan B, Qing Y, Qin X, Prince E, Xie J, Qin H, Huang Y, Li W, Shen C, Sun J, Prakash K, Weng H, Huang H, Chen Z, Zhang B, Wu X, Olsen M, Müschen M, Marcucci G, Ravi S, Li L, Yang C, Li Z, Mulloy J, Wei M, Horne D, Chen J. Effective Novel Fto Inhibitors Show Potent Anti-Cancer Efficacy and Suppress Drug Resistance. Blood 2019, 134: 233. DOI: 10.1182/blood-2019-124535.Peer-Reviewed Original ResearchAML cell linesAnti-leukemic effectsAML cellsMouse modelDrug resistanceAcute myeloid leukemia patientsPotent anti-leukemic effectCell linesPotent anti-cancer efficacyAML cell viabilitySuppress drug resistanceAML mouse modelAnti-leukemia effectMyeloid leukemia patientsAnti-leukemic efficacyTransplantation mouse modelMurine AML cellsOnset of leukemiaFTO inhibitorsPotent therapeutic efficacyTyrosine kinase inhibitorsXenograft mouse modelAnti-leukemic activityFTO proteinAnti-AML efficacy
2016
Phosphorylation of a constrained azacyclic FTY720 analog enhances anti-leukemic activity without inducing S1P receptor activation
McCracken A, McMonigle R, Tessier J, Fransson R, Perryman M, Chen B, Keebaugh A, Selwan E, Barr S, Kim S, Roy S, Liu G, Fallegger D, Sernissi L, Brandt C, Moitessier N, Snider A, Clare S, Müschen M, Huwiler A, Kleinman M, Hanessian S, Edinger A. Phosphorylation of a constrained azacyclic FTY720 analog enhances anti-leukemic activity without inducing S1P receptor activation. Leukemia 2016, 31: 669-677. PMID: 27573555, PMCID: PMC5332311, DOI: 10.1038/leu.2016.244.Peer-Reviewed Original ResearchConceptsS1P receptor activationAnti-leukemic actionProtein phosphatase 2APro-apoptotic targetsPhosphatase 2ASphingosine kinase 2Efficient phosphorylationGenetic approachesReceptor activationKinase 2Nutrient accessChemical biologyPhosphorylationTight inverse correlationDistinct mechanismsS1P receptorsAnti-leukemic activityNovel therapeutic approachesLeukemia progressionReceptor activityMRNA expressionAnti-leukemic agentsActivationEnhanced potencyBiology