2018
First-in-Class ERK1/2 Inhibitor Ulixertinib (BVD-523) in Patients with MAPK Mutant Advanced Solid Tumors: Results of a Phase I Dose-Escalation and Expansion Study
Sullivan RJ, Infante JR, Janku F, Wong DJL, Sosman JA, Keedy V, Patel MR, Shapiro GI, Mier JW, Tolcher AW, Wang-Gillam A, Sznol M, Flaherty K, Buchbinder E, Carvajal RD, Varghese AM, Lacouture ME, Ribas A, Patel SP, DeCrescenzo GA, Emery CM, Groover AL, Saha S, Varterasian M, Welsch DJ, Hyman DM, Li BT. First-in-Class ERK1/2 Inhibitor Ulixertinib (BVD-523) in Patients with MAPK Mutant Advanced Solid Tumors: Results of a Phase I Dose-Escalation and Expansion Study. Cancer Discovery 2018, 8: 184-195. PMID: 29247021, DOI: 10.1158/2159-8290.cd-17-1119.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAminopyridinesFemaleHumansMagnetic Resonance ImagingMaleMiddle AgedMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Mitogen-Activated Protein KinasesMutationNeoplasm StagingNeoplasmsProtein Kinase InhibitorsPyrrolesTomography, X-Ray ComputedTreatment OutcomeYoung AdultConceptsCommon treatment-related adverse eventsSolid tumorsHuman dose-escalation studyMulticenter phase I trialTreatment-related adverse eventsDose-escalation cohortsDose-expansion cohortsMutant solid tumorsPhase II doseAcceptable safety profileAdvanced solid tumorsDose-escalation studyPhase I trialPotent preclinical activityTreatment of patientsSolid tumor malignanciesERK1/2 kinase inhibitorEvaluable patientsDose expansionExpansion cohortAdverse eventsPartial responseDose escalationI trialSafety profile
2010
PLX4032, a selective BRAFV600E kinase inhibitor, activates the ERK pathway and enhances cell migration and proliferation of BRAFWT melanoma cells
Halaban R, Zhang W, Bacchiocchi A, Cheng E, Parisi F, Ariyan S, Krauthammer M, McCusker JP, Kluger Y, Sznol M. PLX4032, a selective BRAFV600E kinase inhibitor, activates the ERK pathway and enhances cell migration and proliferation of BRAFWT melanoma cells. Pigment Cell & Melanoma Research 2010, 23: 190-200. PMID: 20149136, PMCID: PMC2848976, DOI: 10.1111/j.1755-148x.2010.00685.x.Peer-Reviewed Original ResearchConceptsMelanoma cellsTumor cellsMelanoma tumor cellsPrimary melanoma cellsMetastatic tumor cellsStatus of mutationsClinical responseRate of proliferationAdvanced lesionsInhibitor PLX4032Kinase inhibitorsPLX4032ERK pathwayCell migrationNRASDownstream effectorsCell adherenceERK1/2CellsProliferationCell cycle controlMobility of cellsActive ERK1/2Therapy