{"doi":"10.1016/j.redox.2020.101485","title":"A small molecule NRF2 activator BC-1901S ameliorates inflammation through DCAF1/NRF2 axis","abstract":"NRF2 is a master regulator of cellular anti-oxidant and anti-inflammatory responses, and strategies to augment NRF2-dependent responses may beneficial in many diseases. Basal NRF2 protein level is constrained by constitutive KEAP1-mediated degradation, but in the presence of electrophiles, NRF2 ubiquitination is inhibited. Impeded NRF2 degradation increases NRF2 protein, resulting in up-regulation of anti-oxidant gene transcription, and decreased inflammation. KEAP1-independent mechanisms regulating NRF2 stability have also been reported. Here we employed an HTS approach and identified a small molecule, BC-1901S, that stabilized NRF2 and increased its activity. BC-1901S activated NRF2 by inhibiting NRF2 ubiquitination in a KEAP1-independent manner. It further increased NRF2-dependent anti-oxidant gene transcription, and exhibited anti-inflammatory effects in vitro and in vivo. Further, we identified a new NRF2-interacting partner, DDB1 and CUL4 Associated Factor 1 (DCAF1), an E3 ligase that targeted NRF2 for proteasomal degradation. Mechanistically, BC-1901S directly bound to DCAF1 and disrupted NRF2/DCAF1 interaction, thus activating NRF2. These findings provide new insights in NRF2 biology and NRF2 based anti-inflammatory therapy.","journal":"Redox Biology","year":2020,"id":99018,"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":30,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9378,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":313758,"name":"John Evankovich","orcid":"0000-0003-2070-0883","position":1,"is_corresponding":false},{"id":344293,"name":"Travis Lear","orcid":"0000-0001-9156-0844","position":2,"is_corresponding":false},{"id":488055,"name":"Ferhan Tuncer","orcid":"0000-0003-4225-8627","position":3,"is_corresponding":false},{"id":489336,"name":"Jason R. Kennerdell","orcid":null,"position":4,"is_corresponding":false},{"id":488056,"name":"Daniel P. Camarco","orcid":"0000-0001-7958-0658","position":5,"is_corresponding":false},{"id":489337,"name":"Morgan S. Shishido","orcid":null,"position":6,"is_corresponding":false},{"id":488057,"name":"Yuan Liu","orcid":"0000-0001-5031-7514","position":7,"is_corresponding":false},{"id":344301,"name":"Bill B. Chen","orcid":"0000-0003-2695-5107","position":8,"is_corresponding":false},{"id":488054,"name":"Yanwen Chen","orcid":"0000-0002-3467-2871","position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":null,"created_at":"2026-07-18T22:37:35.547042Z","pmid":"32171724","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":[]}