2019
ARV-110: An oral androgen receptor PROTAC degrader for prostate cancer.
Neklesa T, Snyder L, Willard R, Vitale N, Pizzano J, Gordon D, Bookbinder M, Macaluso J, Dong H, Ferraro C, Wang G, Wang J, Crews C, Houston J, Crew A, Taylor I. ARV-110: An oral androgen receptor PROTAC degrader for prostate cancer. Journal Of Clinical Oncology 2019, 37: 259-259. DOI: 10.1200/jco.2019.37.7_suppl.259.Peer-Reviewed Original ResearchAndrogen receptorAR degradationProstate cancerAR proteinAR target gene PSADegradation of ARCastration-resistant prostate cancerAR target gene expressionIND-enabling studiesMajority of patientsProstate cancer patientsMouse xenograft studiesPreclinical efficacy studiesProstate cancer modelMutant AR proteinAndrogen environmentMetastatic diseaseMost patientsAR signalingCancer patientsPreclinical dataAR pathwayMechanisms of resistanceLow nanomolar concentrationsFIH studies
2018
An oral androgen receptor PROTAC degrader for prostate cancer.
Neklesa T, Snyder L, Willard R, Vitale N, Raina K, Pizzano J, Gordon D, Bookbinder M, Macaluso J, Dong H, Liu Z, Ferraro C, Wang G, Wang J, Crews C, Houston J, Crew A, Taylor I. An oral androgen receptor PROTAC degrader for prostate cancer. Journal Of Clinical Oncology 2018, 36: 381-381. DOI: 10.1200/jco.2018.36.6_suppl.381.Peer-Reviewed Original ResearchAndrogen receptorProstate cancerAR proteinAR target gene PSADegradation of AREnzalutamide-Resistant Prostate CancerCastration-resistant prostate cancerAR degradationMajority of patientsMouse xenograft studiesPreclinical efficacy studiesMutant AR proteinNon-rodent speciesAndrogen environmentMetastatic diseaseMost patientsAR signalingPreclinical dataAR pathwayMechanisms of resistanceDrug exposureXenograft studiesVCaP cellsEfficacy studiesExploratory toxicology studies
2017
An oral androgen receptor PROTAC degrader for prostate cancer.
Neklesa T, Snyder L, Bookbinder M, Chen X, Crew A, Crews C, Dong H, Gordon D, Raina K, Rossi A, Taylor I, Vitale N, Wang J, Willard R, Zimmermann K. An oral androgen receptor PROTAC degrader for prostate cancer. Journal Of Clinical Oncology 2017, 35: 273-273. DOI: 10.1200/jco.2017.35.6_suppl.273.Peer-Reviewed Original ResearchAndrogen receptorAR degradationProstate cancerAR proteinAR target gene PSADegradation of ARCastration-resistant prostate cancerTotal androgen receptorMajority of patientsMutant AR proteinTumor growth inhibitionVivo preclinical studiesCell linesInhibits cell proliferationVCaP xenograftsMetastatic diseaseMost patientsAR pathwayElevated androgensMechanisms of resistancePreclinical studiesXenograft studiesVCaP cellsOral bioavailabilityPotent apoptosis
2015
Small‐Molecule‐Mediated Degradation of the Androgen Receptor through Hydrophobic Tagging
Gustafson J, Neklesa T, Cox C, Roth A, Buckley D, Tae H, Sundberg T, Stagg D, Hines J, McDonnell D, Norris J, Crews C. Small‐Molecule‐Mediated Degradation of the Androgen Receptor through Hydrophobic Tagging. Angewandte Chemie 2015, 127: 9795-9798. DOI: 10.1002/ange.201503720.Peer-Reviewed Original ResearchSelective androgen receptor degradersAndrogen receptorAR mutationsAndrogen-dependent prostate cancer cell lineSecond-generation AR antagonistsAR degradationProstate tumor cell proliferationProstate cancer cell linesAR target genesTumor cell proliferationAntitumor chemotherapeutic agentsCancer cell linesAR antagonistsChemotherapeutic agentsCell proliferationAR ligandsCell linesAntagonistTumor strategyResistance mechanismsReceptorsRecent studiesProliferationTarget genesDependent transcriptionSmall‐Molecule‐Mediated Degradation of the Androgen Receptor through Hydrophobic Tagging
Gustafson JL, Neklesa TK, Cox CS, Roth AG, Buckley DL, Tae HS, Sundberg TB, Stagg DB, Hines J, McDonnell DP, Norris JD, Crews CM. Small‐Molecule‐Mediated Degradation of the Androgen Receptor through Hydrophobic Tagging. Angewandte Chemie International Edition 2015, 54: 9659-9662. PMID: 26083457, PMCID: PMC4547777, DOI: 10.1002/anie.201503720.Peer-Reviewed Original ResearchMeSH KeywordsAndrogen Receptor AntagonistsAntineoplastic AgentsBenzamidesCell Line, TumorCell ProliferationDrug Resistance, NeoplasmHumansHydrophobic and Hydrophilic InteractionsMaleNitrilesPhenylthiohydantoinPoint MutationProstateProstatic NeoplasmsProteolysisReceptors, AndrogenSmall Molecule LibrariesConceptsSelective androgen receptor degradersAndrogen receptorAR mutationsAndrogen-dependent prostate cancer cell lineSecond-generation AR antagonistsAR degradationProstate tumor cell proliferationProstate cancer cell linesAR target genesTumor cell proliferationAntitumor chemotherapeutic agentsCancer cell linesAR antagonistsChemotherapeutic agentsCell proliferationAR ligandsCell linesAntagonistTumor strategyResistance mechanismsReceptorsRecent studiesProliferationTarget genesDependent transcription