2015
A Novel Small-Molecule Inhibitor Targeting CREB-CBP Complex Possesses Anti-Cancer Effects along with Cell Cycle Regulation, Autophagy Suppression and Endoplasmic Reticulum Stress
Lee JW, Park HS, Park SA, Ryu SH, Meng W, Jürgensmeier JM, Kurie JM, Hong WK, Boyer JL, Herbst RS, Koo JS. A Novel Small-Molecule Inhibitor Targeting CREB-CBP Complex Possesses Anti-Cancer Effects along with Cell Cycle Regulation, Autophagy Suppression and Endoplasmic Reticulum Stress. PLOS ONE 2015, 10: e0122628. PMID: 25897662, PMCID: PMC4405579, DOI: 10.1371/journal.pone.0122628.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdenocarcinoma of LungAnilidesAntineoplastic AgentsApoptosis Regulatory ProteinsAutophagyAutophagy-Related Protein 7Bcl-2-Like Protein 11Cell Cycle CheckpointsCell Line, TumorCyclic AMP Response Element-Binding ProteinDrug Screening Assays, AntitumorEndoplasmic Reticulum StressHumansInhibitory Concentration 50Kaplan-Meier EstimateLung NeoplasmsMembrane ProteinsMolecular Docking SimulationOrganophosphatesPeptide FragmentsProportional Hazards ModelsProtein BindingProto-Oncogene ProteinsSialoglycoproteinsUbiquitin-Activating EnzymesConceptsLung cancerHuman lung cancer cell linesEndoplasmic reticulum (ER) stress markersLung cancer cell linesNovel therapeutic strategiesPotential therapeutic targetAnti-cancer effectsNovel small molecule inhibitorPotential therapeutic agentCyclic AMP response element binding proteinAccumulation of p62Response element-binding proteinEndoplasmic reticulum stressCancer cell linesCancer deathCommon subtypeCell cycle arrestLung adenocarcinomaNew therapiesTherapeutic strategiesSmall molecule inhibitorsTherapeutic targetElement-binding proteinStress markersTherapeutic agents
2010
Molecular Pharmacology and Antitumor Activity of PHT-427, a Novel Akt/Phosphatidylinositide-Dependent Protein Kinase 1 Pleckstrin Homology Domain Inhibitor
Meuillet EJ, Zuohe S, Lemos R, Ihle N, Kingston J, Watkins R, Moses SA, Zhang S, Du-Cuny L, Herbst R, Jacoby JJ, Zhou LL, Ahad AM, Mash EA, Kirkpatrick DL, Powis G. Molecular Pharmacology and Antitumor Activity of PHT-427, a Novel Akt/Phosphatidylinositide-Dependent Protein Kinase 1 Pleckstrin Homology Domain Inhibitor. Molecular Cancer Therapeutics 2010, 9: 706-717. PMID: 20197390, PMCID: PMC2837366, DOI: 10.1158/1535-7163.mct-09-0985.Peer-Reviewed Original ResearchMeSH Keywords3-Phosphoinositide-Dependent Protein KinasesAnimalsAntineoplastic AgentsFemaleHumansMiceMice, Inbred C57BLMice, NudeModels, BiologicalOncogene Protein v-aktProtein BindingProtein Interaction Domains and MotifsProtein Kinase InhibitorsProtein Serine-Threonine KinasesSulfonamidesThiadiazolesTumor Cells, CulturedXenograft Model Antitumor AssaysConceptsAntitumor activityTumor xenograftsNon-small cell lung cancerMolecular pharmacologyCell lung cancerAdditive antitumor activityHuman tumor xenograftsPHT-427K-ras mutant tumorsVivo antitumor activityLung cancerSensitive tumorsPIK3CA mutationsBreast cancerImmunodeficient miceBlood chemistryMutant tumorsCombination studiesResistant cellsMinimal toxicityWeight lossTumorsCancerCancer cellsAkt inhibition