{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Thomas E"],"funding":["Maryland Department of Health’s Cigarette Restitution Fund Program and the National Cancer Institute—Cancer Center Support Grant","National Cancer Institute","NCI NIH HHS","National Institutes of Health"],"pagination":["2699"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9454942"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["11(17)"],"pubmed_abstract":["Prostate cancer (PCa) relies in part on AR-signaling for disease development and progression. Earlier, we developed drug candidate galeterone, which advanced through phase 2-clinical trials in treating castration-resistant PCa (CRPC). Subsequently, we designed, synthesized, and evaluated next-generation galeterone-analogs including VNPP433-3β which is potently efficacious against pre-clinical models of PCa. This study describes the mechanism of action of VNPP433-3β that promotes degradation of full-length AR (fAR) and its splice variant AR-V7 besides depleting MNK1/2 in in vitro and in vivo CRPC models that stably overexpresses fAR. VNPP433-3β directly engages AR within the cell and promotes proteasomal degradation of fAR and its splice variant AR-V7 by enhancing the interaction of AR with"],"journal":["Cells"],"pubmed_title":["Novel AR/AR-V7 and Mnk1/2 Degrader, VNPP433-3β: Molecular Mechanisms of Action and Efficacy in AR-Overexpressing Castration Resistant Prostate Cancer In Vitro and In Vivo Models."],"pmcid":["PMC9454942"],"funding_grant_id":["P30 CA134274","P30CA134274","R01CA224696","R01 CA224696"],"pubmed_authors":["Ambulos NP","Kane MA","Njar VCO","Huang W","Zhang Y","Thomas E","Purushottamachar P","Thankan RS","Weber DJ"],"additional_accession":[]},"is_claimable":false,"name":"Novel AR/AR-V7 and Mnk1/2 Degrader, VNPP433-3β: Molecular Mechanisms of Action and Efficacy in AR-Overexpressing Castration Resistant Prostate Cancer In Vitro and In Vivo Models.","description":"Prostate cancer (PCa) relies in part on AR-signaling for disease development and progression. Earlier, we developed drug candidate galeterone, which advanced through phase 2-clinical trials in treating castration-resistant PCa (CRPC). Subsequently, we designed, synthesized, and evaluated next-generation galeterone-analogs including VNPP433-3β which is potently efficacious against pre-clinical models of PCa. This study describes the mechanism of action of VNPP433-3β that promotes degradation of full-length AR (fAR) and its splice variant AR-V7 besides depleting MNK1/2 in in vitro and in vivo CRPC models that stably overexpresses fAR. VNPP433-3β directly engages AR within the cell and promotes proteasomal degradation of fAR and its splice variant AR-V7 by enhancing the interaction of AR with","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Aug","modification":"2026-04-08T12:09:08.729Z","creation":"2025-02-19T04:38:50.662Z"},"accession":"S-EPMC9454942","cross_references":{"pubmed":["36078112"],"doi":["10.3390/cells11172699"]}}