2021
Mutant-selective degradation by BRAF-targeting PROTACs
Alabi S, Jaime-Figueroa S, Yao Z, Gao Y, Hines J, Samarasinghe KTG, Vogt L, Rosen N, Crews CM. Mutant-selective degradation by BRAF-targeting PROTACs. Nature Communications 2021, 12: 920. PMID: 33568647, PMCID: PMC7876048, DOI: 10.1038/s41467-021-21159-7.Peer-Reviewed Original ResearchConceptsInhibitor-based therapyBRAF inhibitor-based therapiesBRAF missense mutationsCancer cell growthBRAF V600Current treatmentNew therapiesTherapeutic windowXenograft modelBRAF mutantMutant BRAFVivo efficacyDrug modalitiesRaf family membersProteolysis targeting chimera (PROTAC) technologyTherapyBRAFMissense mutationsFamily membersBRAFWTCell growthDegree of selectivityInactivated conformationPatientsV600
2016
ARV-330: Androgen receptor PROTAC degrader for prostate cancer.
Neklesa T, Jin M, Crew A, Rossi A, Willard R, Dong H, Siu K, Wang J, Gordon D, Chen X, Ferraro C, Crews C, Coleman K, Winkler J. ARV-330: Androgen receptor PROTAC degrader for prostate cancer. Journal Of Clinical Oncology 2016, 34: 267-267. DOI: 10.1200/jco.2016.34.2_suppl.267.Peer-Reviewed Original ResearchAndrogen receptorAR mutationsProstate cancerTotal androgen receptorTreatment of miceAR protein levelsProstate cancer cellsGood pharmacokinetic propertiesPlasma PSAMetastatic diseaseNM R1881SC injectionAndrogen productionDisease progressionPSA expressionIntact miceTherapeutic effectCastrated miceVCaP cellsAnimal modelsProstate involutionTumor growthVivo efficacyPreclinical developmentPharmacokinetic properties