{"doi":"10.1021/jm8014525","title":"A Basis for Reduced Chemical Library Inhibition of Firefly Luciferase Obtained from Directed Evolution","abstract":null,"journal":"Journal of Medicinal Chemistry","year":2009,"id":653827,"datarank":4.620473984818751,"base_score":4.430816798843313,"endowment":4.430816798843313,"self_citation_contribution":0.6646225198264971,"citation_network_contribution":3.955851464992253,"self_endowment_contribution":0.6646225198264971,"citer_contribution":3.955851464992253,"corpus_percentile":null,"corpus_rank":null,"citation_count":83,"citer_count":62,"citers_with_citation_signal":58,"citers_with_endowment":58,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1283972,"name":"Ya-Qin Zhang","orcid":"0000-0003-1851-7932","position":1,"is_corresponding":false},{"id":1675767,"name":"Noel T. 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Auld","orcid":"0000-0002-8164-9375","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"A Basis for Reduced Chemical Library Inhibition of Firefly Luciferase Obtained from Directed Evolution","abstract":"We measured the \"druggability\" of the ATP-dependent luciferase derived from the firefly Photuris pennsylvanica that was optimized using directed evolution (Ultra-Glo, Promega). Quantitative high-throughput screening (qHTS) was used to determine IC(50)s of 198899 samples against a formulation of Ultra-Glo luciferase (Kinase-Glo). We found that only 0.1% of the Kinase-Glo inhibitors showed an IC(50) < 10 microM compared to 0.9% found from a previous qHTS against the firefly luciferase from Photinus pyralis (lucPpy). Further, the maximum affinity identified in the lucPpy qHTS was 50 nM, while for Kinase-Glo this value increased to 600 nM. Compounds with interactions stretching outside the luciferin binding pocket were largely lost with Ultra-Glo luciferase. Therefore, Ultra-Glo luciferase will show less compound interference when used as an ATP sensor compared to lucPpy. This study demonstrates the power of large-scale quantitative analysis of structure-activity relationships (>100K compounds) in addressing important questions such as a target's druggability.","is_dataset_classified":null,"base_score":4.430816798843313,"endowment":4.430816798843313,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19215089","pmcid":null,"openalex_id":"https://openalex.org/W2038573181","authors":[],"funders":[],"total_grants":0,"fwci":4.4114,"citation_percentile":0.95396152,"influential_citations":0,"citation_trend":[{"year":2012,"count":5},{"year":2013,"count":5},{"year":2014,"count":5},{"year":2015,"count":5},{"year":2016,"count":5},{"year":2017,"count":6},{"year":2018,"count":1},{"year":2020,"count":6},{"year":2021,"count":4},{"year":2023,"count":3},{"year":2024,"count":4},{"year":2025,"count":3},{"year":2026,"count":1}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://doi.org/10.7270/q2xd11pw","host_type":"repository"},{"url":"https://doi.org/10.7270/q2xd11pw","host_type":"repository"},{"url":"https://pubs.acs.org/doi/pdf/10.1021/jm8014525","host_type":"publisher"},{"url":"https://doi.org/10.1021/jm8014525","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/19215089","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3430137","host_type":"repository"}],"fields_of_study":["bioluminescence and chemiluminescence research","Neurobiology and Insect Physiology Research","Photoreceptor and optogenetics research"],"mesh_terms":["Adenosine Triphosphate","Animals","Binding Sites","Enzyme Inhibitors","Luminescent Measurements","Models, Molecular","Oxadiazoles","Quantitative Structure-Activity Relationship","Fireflies","Luciferases, Firefly","Firefly Luciferin","Benzothiazoles","High-Throughput Screening Assays"],"keywords":["Luciferase","Druggability","Luciferin","Chemistry","Kinase","Bioluminescence","Firefly protocol","Lampyridae","Biochemistry","Transfection","Biology"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-11T01:14:36.092535Z","pmid":null,"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":[]}