{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Ng YLD"],"funding":["Deutsche Forschungsgemeinschaft","Javna Agencija za Raziskovalno Dejavnost RS","NCI NIH HHS"],"pagination":["4703-4733"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10108347"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["66(7)"],"pubmed_abstract":["Proteolysis targeting chimeras (PROTACs) represent a new pharmacological modality to inactivate disease-causing proteins. PROTACs operate via recruiting E3 ubiquitin ligases, which enable the transfer of ubiquitin tags onto their target proteins, leading to proteasomal degradation. However, several E3 ligases are validated pharmacological targets themselves, of which inhibitor of apoptosis (IAP) proteins are considered druggable in cancer. Here, we report three series of heterobifunctional PROTACs, which consist of an IAP antagonist linked to either von Hippel-Lindau- or cereblon-recruiting ligands. Hijacking E3 ligases against each other led to potent, rapid, and preferential depletion of cellular IAPs. In addition, these compounds caused complete X-chromosome-linked IAP knockdown, which "],"journal":["Journal of medicinal chemistry"],"pubmed_title":["Heterobifunctional Ligase Recruiters Enable pan-Degradation of Inhibitor of Apoptosis Proteins."],"pmcid":["PMC10108347"],"funding_grant_id":["R01 CA214608","R01 CA218278","Kr-3886/2-1","P1-0208","J1-2485","SFB-1074"],"pubmed_authors":["Bricelj A","Gutschow M","Kronke J","Murgai A","Jansen JA","Donovan KA","Steinebach C","Peter K","Sosic I","Ng YLD"],"additional_accession":[]},"is_claimable":false,"name":"Heterobifunctional Ligase Recruiters Enable pan-Degradation of Inhibitor of Apoptosis Proteins.","description":"Proteolysis targeting chimeras (PROTACs) represent a new pharmacological modality to inactivate disease-causing proteins. PROTACs operate via recruiting E3 ubiquitin ligases, which enable the transfer of ubiquitin tags onto their target proteins, leading to proteasomal degradation. However, several E3 ligases are validated pharmacological targets themselves, of which inhibitor of apoptosis (IAP) proteins are considered druggable in cancer. Here, we report three series of heterobifunctional PROTACs, which consist of an IAP antagonist linked to either von Hippel-Lindau- or cereblon-recruiting ligands. Hijacking E3 ligases against each other led to potent, rapid, and preferential depletion of cellular IAPs. In addition, these compounds caused complete X-chromosome-linked IAP knockdown, which ","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Apr","modification":"2025-04-04T22:59:38.49Z","creation":"2025-04-04T22:59:38.49Z"},"accession":"S-EPMC10108347","cross_references":{"pubmed":["36996313"],"doi":["10.1021/acs.jmedchem.2c01817"]}}