{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE341nnn/GSE341230/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE341230"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Disrupting BRD4-BD1–p62 Engagement Restores Protective Autophagy [RNA-seq]","description":"Impaired protective autophagy contributes to idiopathic pulmonary fibrosis (IPF), yet therapeutic strategies that restore this process remain limited. Here, we identify SKLB-39b, a BRD4-BD1-selective inhibitor that restores protective autophagy and attenuates pulmonary fibrosis. SKLB-39b exhibits over 100-fold selectivity for BRD4-BD1 relative to BRD4-BD2 and nearly 10-fold greater affinity for BRD4-BD1 than for BRD2/3-BD1. Mechanistically, we identify a BRD4-BD1-p62 interaction that links BET bromodomain function to autophagy regulation. By engaging Leu92 and Ile146 through a hydrophobic binding mode, SKLB-39b disrupts this interaction, restores ULK1-dependent autophagy, and provides a structural framework for BD1-selective inhibitor design. SKLB-39b outperformed JQ-1 in suppressing fibroblast activation, epithelial-mesenchymal transition, and collagen deposition in experimental fibrosis while showing favorable pharmacokinetic exposure and no overt toxicity in the mouse studies performed. These findings establish the BRD4-BD1-p62 interface as a druggable target for restoring protective autophagy in IPF.","dates":{"publication":"2026/08/17"},"accession":"GSE341230","cross_references":{"GSM":["GSM9902472","GSM9902473","GSM9902474","GSM9902475","GSM9902470","GSM9902471","GSM9902476","GSM9902477","GSM9902478"],"GPL":["24676"],"GSE":["341230"],"taxon":["Homo sapiens"]}}