{"doi":"10.1021/acsptsci.5c00412","title":"An Assessment of Kinase Selectivity, Enzyme Inhibition Kinetics and in Vitro Activity for Several Bruton Tyrosine Kinase (BTK) Inhibitors","abstract":"Inhibitors of the Bruton's tyrosine kinase (BTK) are of broad utility in the treatment of multiple diseases including several B-cell malignancies via effective blockade of oncogenic B-cell receptor (BCR) signaling. BTK is a cytoplasmic tyrosine kinase which harbors a targetable cysteine residue (Cys481) and the majority of BTK inhibitors are covalent modifiers directed at this position. Despite possessing a common mechanism of action, BTK inhibitors differ in key attributes including off-target kinome profiles, tolerability, pharmacokinetics and the underlying BTK inhibition kinetics. These characteristics play a significant role in the ultimate utility of these drugs. Herein, we compare several clinically active BTK inhibitors in biochemical and in vitro assays to gain a broader appreciation of the similarities and differences that govern the success of this important drug class. The combined datasets highlight that each agent has excellent on-target potency and good BTK selectivity. The data further suggests an association between optimized BTK inhibition kinetics and in vitro cytotoxicity profiles.","journal":"ACS Pharmacology & Translational Science","year":2025,"id":535427,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9657,"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":378051,"name":"Xiaohu Zhang","orcid":"0000-0002-5329-1599","position":1,"is_corresponding":false},{"id":1087011,"name":"Patricia Alfonso","orcid":null,"position":2,"is_corresponding":false},{"id":449146,"name":"Patrick J. Morris","orcid":"0000-0003-2380-4178","position":3,"is_corresponding":false},{"id":287620,"name":"Carleen Klumpp‐Thomas","orcid":"0000-0002-6646-6132","position":4,"is_corresponding":false},{"id":258330,"name":"Christopher Melani","orcid":"0000-0002-9661-4570","position":5,"is_corresponding":false},{"id":625528,"name":"Crystal McKnight","orcid":"0009-0007-6554-5772","position":6,"is_corresponding":false},{"id":106819,"name":"James D. Phelan","orcid":"0000-0001-8950-2485","position":7,"is_corresponding":false},{"id":565716,"name":"David O. Holland","orcid":"0000-0002-6742-6546","position":8,"is_corresponding":false},{"id":339280,"name":"Kelli M. Wilson","orcid":"0000-0003-2636-2766","position":9,"is_corresponding":false},{"id":467528,"name":"Scott B. Hoyt","orcid":"0009-0009-9788-1935","position":10,"is_corresponding":false},{"id":233601,"name":"Mark Roschewski","orcid":"0000-0003-0278-2635","position":11,"is_corresponding":false},{"id":22118,"name":"Peter J. Tonge","orcid":"0000-0003-1606-3471","position":12,"is_corresponding":false},{"id":35694,"name":"Wyndham H. Wilson","orcid":"0000-0002-2862-9711","position":13,"is_corresponding":false},{"id":261945,"name":"Michele Ceribelli","orcid":"0000-0001-9857-9521","position":14,"is_corresponding":false},{"id":35688,"name":"Louis M. Staudt","orcid":"0000-0002-1735-2892","position":15,"is_corresponding":false},{"id":258191,"name":"Craig J. Thomas","orcid":"0000-0001-9386-9001","position":16,"is_corresponding":false},{"id":1086449,"name":"Ana Corrionero","orcid":"0009-0002-9990-1214","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:51:56.297114Z","pmid":"41409161","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":[]}