{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Chatterjee BK"],"funding":["NIGMS NIH HHS"],"pubmed_abstract":["The AMP transferase, FICD, is an emerging drug target finetuning stress signaling in the endoplasmic reticulum (ER). FICD is a bi-functional 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 to 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 efficiently inhibit pathogenic FICD variants and improve proinsulin processing in β cells. Our study identifies and valid"],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2024.07.13.603377"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11275912"],"repository":["biostudies-literature"],"pubmed_title":["Small molecule FICD inhibitors suppress endogenous and pathologic FICD-mediated protein AMPylation."],"pmcid":["PMC11275912"],"funding_grant_id":["R35 GM142561"],"pubmed_authors":["Chakravorty A","Truttmann MC","Brooks CL","Lacy SM","Rech J","Arvan PD","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 finetuning stress signaling in the endoplasmic reticulum (ER). FICD is a bi-functional 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 to 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 efficiently inhibit pathogenic FICD variants and improve proinsulin processing in β cells. Our study identifies and valid","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Jul","modification":"2026-04-07T21:03:30.537Z","creation":"2025-04-04T02:46:38.481Z"},"accession":"S-EPMC11275912","cross_references":{"pubmed":["39071275"],"doi":["10.1101/2024.07.13.603377"]}}