{"doi":"10.1039/d1md00062d","title":"Deglycase-activity oriented screening to identify DJ-1 inhibitors","abstract":"The oncoprotein and Parkinson's disease-associated enzyme DJ-1/PARK7 has emerged as a promiscuous deglycase that can remove methylglyoxal-induced glycation adducts from both proteins and nucleotides. However, dissecting its structural and enzymatic functions remains a challenge due to the lack of potent, specific, and pharmacokinetically stable inhibitors targeting its catalytic site (including Cys106). To evaluate potential drug-like leads against DJ-1, we leveraged its deglycase activity in an enzyme-coupled, fluorescence lactate-detection assay based on the recent understanding of its deglycation mechanism. In addition, we developed assays to directly evaluate DJ-1's esterase activity using both colorimetric and fluorescent substrates. The resulting optimized assay was used to evaluate a library of potential reversible and irreversible DJ-1 inhibitors. The deglycase activity-oriented screening strategy described herein establishes a new platform for the discovery of potential anti-cancer drugs.","journal":"RSC Medicinal Chemistry","year":2021,"id":176443,"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":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9567,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":718988,"name":"Efrat Finkin-Groner","orcid":"0000-0002-1458-7098","position":1,"is_corresponding":false},{"id":568254,"name":"Yoshiyuki Fukase","orcid":"0000-0001-8088-2522","position":2,"is_corresponding":false},{"id":289012,"name":"Qingfei Zheng","orcid":"0000-0002-8397-3507","position":3,"is_corresponding":false},{"id":290023,"name":"Shan Sun","orcid":"0000-0001-8838-3226","position":4,"is_corresponding":false},{"id":611060,"name":"Mayako Michino","orcid":"0000-0002-5469-025X","position":5,"is_corresponding":false},{"id":718989,"name":"David J. Huggins","orcid":"0000-0003-1579-2496","position":6,"is_corresponding":false},{"id":718990,"name":"Robert W. Myers","orcid":"0000-0003-2599-1050","position":7,"is_corresponding":false},{"id":237419,"name":"Yael David","orcid":"0000-0003-1696-0025","position":8,"is_corresponding":false},{"id":289013,"name":"Igor Maksimovic","orcid":"0000-0002-4379-6884","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-18T23:47:23.605867Z","pmid":"34355187","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":[]}