Featured Publications
Induced protein degradation: an emerging drug discovery paradigm
Lai AC, Crews CM. Induced protein degradation: an emerging drug discovery paradigm. Nature Reviews Drug Discovery 2016, 16: 101-114. PMID: 27885283, PMCID: PMC5684876, DOI: 10.1038/nrd.2016.211.Peer-Reviewed Original ResearchConceptsProteolysis-targeting chimaerasProtein degradationUndruggable proteomeTarget protein degradationDifferent E3 ligasesInhibitor-based approachE3 ligasesDrug discovery platformProtein targetsProteomeDiscovery platformProtein expressionDrug discovery paradigmInhibition approachCell culturesDiscovery paradigmLigasesExact mechanismDegradationMouse modelDegradersProteinChimaerasPicomolar potency
2017
BRD4 Proteolysis Targeting Chimera (PROTAC) ARV-825 Targets Both NOTCH1-MYC Regulatory Circuit and Leukemia-Microenvironment in T-ALL
Piya S, Mu H, Bhattacharya S, McQueen T, Davis R, Ruvolo V, Baran N, Qian Y, Raina K, Crews C, You M, McKay P, Konopleva M, Kantarjian H, Andreeff M, Borthakur G. BRD4 Proteolysis Targeting Chimera (PROTAC) ARV-825 Targets Both NOTCH1-MYC Regulatory Circuit and Leukemia-Microenvironment in T-ALL. Blood 2017, 130: 716. DOI: 10.1182/blood.v130.suppl_1.716.716.Peer-Reviewed Original ResearchT-cell acute lymphoblastic leukemiaAcute lymphoblastic leukemiaLymphoblastic leukemiaARV-825PI3K/AktGamma-secretase inhibitorsMouse modelRelapsed T-cell acute lymphoblastic leukemiaVehicle-treated control micePatient-derived xenograft mouse modelsCell linesLow leukemia burdenCell acute lymphoblastic leukemiaReactive oxygen speciesT-cell lymphoblastic leukemiaAnti-leukemic effectsXenograft mouse modelLeukemia-stroma interactionsPDX mouse modelsBristol-Meyers SquibbG1/S cell cycle progressionPersistence of diseaseAttractive therapeutic targetIntra-cellular reactive oxygen speciesMicroenvironmental signals