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