{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Swartzel JC"],"funding":["American Cancer Society","Japan Agency for Medical Research and Development","National Cancer Institute","NCI NIH HHS","NIGMS NIH HHS","Japan Society for the Promotion of Science"],"pagination":["1789-1798"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10367122"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["17(7)"],"pubmed_abstract":["The RNA decapping scavenger protein, DcpS, has recently been identified as a dependency in acute myeloid leukemia (AML). The potent DcpS inhibitor RG3039 attenuates AML cell viability, and shRNA knockdown of DcpS is also antiproliferative. Importantly, DcpS was found to be non-essential in normal human hematopoietic cells, which opens a therapeutic window for AML treatment by DcpS modulation. Considering this strong DcpS dependence in AML cell lines, we explored PROTAC-mediated degradation as an alternative strategy to modulate DcpS activity. Herein, we report the development of JCS-1, a PROTAC exhibiting effective degradation of DcpS at nanomolar concentrations. JCS-1 non-covalently binds DcpS with a RG3039-based warhead and recruits the E3 ligase VHL, which induces potent, rapid, and sus"],"journal":["ACS chemical biology"],"pubmed_title":["Targeted Degradation of mRNA Decapping Enzyme DcpS by a VHL-Recruiting PROTAC."],"pmcid":["PMC10367122"],"funding_grant_id":["18063889","R35CA197589","F31 CA232477","R35 CA197589","20H05699","T32 GM067543","F31CA232477"],"pubmed_authors":["Carder EJ","Daftary M","Maeda T","Swartzel JC","Crews CM","Bond MJ","Zimmer JT","Pintado-Urbanc AP","Douglas T","Krone MW","Simon MD"],"additional_accession":[]},"is_claimable":false,"name":"Targeted Degradation of mRNA Decapping Enzyme DcpS by a VHL-Recruiting PROTAC.","description":"The RNA decapping scavenger protein, DcpS, has recently been identified as a dependency in acute myeloid leukemia (AML). The potent DcpS inhibitor RG3039 attenuates AML cell viability, and shRNA knockdown of DcpS is also antiproliferative. Importantly, DcpS was found to be non-essential in normal human hematopoietic cells, which opens a therapeutic window for AML treatment by DcpS modulation. Considering this strong DcpS dependence in AML cell lines, we explored PROTAC-mediated degradation as an alternative strategy to modulate DcpS activity. Herein, we report the development of JCS-1, a PROTAC exhibiting effective degradation of DcpS at nanomolar concentrations. JCS-1 non-covalently binds DcpS with a RG3039-based warhead and recruits the E3 ligase VHL, which induces potent, rapid, and sus","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Jul","modification":"2026-04-12T23:14:40.967Z","creation":"2025-02-19T01:18:09.172Z"},"accession":"S-EPMC10367122","cross_references":{"pubmed":["35749470"],"doi":["10.1021/acschembio.2c00145"]}}