{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Chatterjee BK"],"funding":["University of Michigan","NIDDK NIH HHS","National Institute of Diabetes and Digestive and Kidney Diseases","National Institute of General Medical Sciences","NIGMS NIH HHS","NIH HHS","Life Sciences Institute"],"pagination":["880-895"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12007993"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["20(4)"],"pubmed_abstract":["The AMP transferase, FICD, is an emerging drug target fine-tuning stress signaling in the endoplasmic reticulum (ER). FICD is a bifunctional enzyme, catalyzing both AMP addition (AMPylation) and removal (deAMPylation) from the ER-resident chaperone BiP/GRP78. Despite increasing evidence linking excessive BiP/GRP78 AMPylation to human diseases, small molecules that inhibit pathogenic FICD variants are lacking. Using an <i>in vitro</i> high-throughput screen, we identify two small-molecule FICD inhibitors, C22 and C73. Both molecules significantly inhibit FICD-mediated BiP/GRP78 AMPylation in intact cells while only weakly inhibiting BiP/GRP78 deAMPylation. C22 and C73 also inhibit pathogenic FICD variants and improve proinsulin processing in β cells. Our study identifies and validates FICD "],"journal":["ACS chemical biology"],"pubmed_title":["Small-Molecule FICD Inhibitors Suppress Endogenous and Pathologic FICD-Mediated Protein AMPylation."],"pmcid":["PMC12007993"],"funding_grant_id":["NIHDK48280","S10 OD034346","P30 DK020572","R35 GM130587","1R35GM142561","R35GM130597","R01 DK048280","R35 GM142561"],"pubmed_authors":["Chakravorty A","Truttmann MC","Brooks CL","Lacy SM","Giblin W","Arvan P","Rech J","Chatterjee BK","Alam M"],"additional_accession":[]},"is_claimable":false,"name":"Small-Molecule FICD Inhibitors Suppress Endogenous and Pathologic FICD-Mediated Protein AMPylation.","description":"The AMP transferase, FICD, is an emerging drug target fine-tuning stress signaling in the endoplasmic reticulum (ER). FICD is a bifunctional enzyme, catalyzing both AMP addition (AMPylation) and removal (deAMPylation) from the ER-resident chaperone BiP/GRP78. Despite increasing evidence linking excessive BiP/GRP78 AMPylation to human diseases, small molecules that inhibit pathogenic FICD variants are lacking. Using an <i>in vitro</i> high-throughput screen, we identify two small-molecule FICD inhibitors, C22 and C73. Both molecules significantly inhibit FICD-mediated BiP/GRP78 AMPylation in intact cells while only weakly inhibiting BiP/GRP78 deAMPylation. C22 and C73 also inhibit pathogenic FICD variants and improve proinsulin processing in β cells. Our study identifies and validates FICD ","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Apr","modification":"2026-06-01T05:54:03.033Z","creation":"2025-07-03T03:04:34.217Z"},"accession":"S-EPMC12007993","cross_references":{"pubmed":["40036289"],"doi":["10.1021/acschembio.4c00847"]}}