{"doi":"10.1039/d5cb00125k","title":"Application of HIV-1 viral protein R-derived-peptides as new E3 ligase-binding components of BRD4 degraders","abstract":"the UPS. We envisioned that Vpr fragments may function in PROTACs as new E3 ligase-binding ligands. Herein, we designed, synthesized and evaluated bromodomain 4 (BRD4)-targeting PROTACs (BRD4-PROTACs) that employ a well-known BRD4 inhibitor (JQ1) as a warhead and Vpr-derived peptides as the E3 ligase-binding ligands. We successfully demonstrate that the Vpr-derived peptides can function as E3 ligase-targeting ligands for PROTAC development. We also evaluated PROTACs based on the HIV-1 latency-reversing activity of JQ-1. The chemical degraders are less effective than the parent inhibitor as a latency-reversing agent (LRA). However, the low cytotoxicity of the new peptidic PROTACs allowed the compounds to be tolerated at high does, leading to potent LRA activity.","journal":"RSC Chemical Biology","year":2025,"id":579414,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9551,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1489616,"name":"Xueyuan Huang","orcid":"0000-0001-5738-9086","position":1,"is_corresponding":false},{"id":1490017,"name":"Maho Miyamoto","orcid":null,"position":2,"is_corresponding":false},{"id":454026,"name":"Sayaka Sukegawa","orcid":null,"position":3,"is_corresponding":false},{"id":1489617,"name":"Hidetomo Yokoo","orcid":"0000-0002-9354-6592","position":4,"is_corresponding":false},{"id":1489618,"name":"Hiroaki Takeuchi","orcid":"0000-0002-5689-9858","position":5,"is_corresponding":false},{"id":1489619,"name":"Yosuke Demizu","orcid":"0000-0001-7521-4861","position":6,"is_corresponding":false},{"id":588041,"name":"Hirokazu Tamamura","orcid":"0000-0003-2788-2579","position":7,"is_corresponding":false},{"id":367621,"name":"Kohei Tsuji","orcid":"0000-0003-4773-8793","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-19T02:58:30.282164Z","pmid":"41170202","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}