{"doi":"10.1016/j.bmc.2019.05.050","title":"Opportunities and challenges for the development of covalent chemical immunomodulators","abstract":null,"journal":"Bioorganic & Medicinal Chemistry","year":2019,"id":657404,"datarank":1.0314361730461294,"base_score":3.091042453358316,"endowment":3.091042453358316,"self_citation_contribution":0.4636563680037475,"citation_network_contribution":0.5677798050423819,"self_endowment_contribution":0.4636563680037475,"citer_contribution":0.5677798050423819,"corpus_percentile":null,"corpus_rank":null,"citation_count":21,"citer_count":18,"citers_with_citation_signal":16,"citers_with_endowment":16,"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":1132670,"name":"Jian Cao","orcid":"0000-0001-9395-0387","position":1,"is_corresponding":false},{"id":693667,"name":"Sean M. Maddox","orcid":"0000-0001-5164-1789","position":2,"is_corresponding":false},{"id":377194,"name":"Keriann M. Backus","orcid":"0000-0001-8541-1404","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Opportunities and challenges for the development of covalent chemical immunomodulators","abstract":"Compounds that react irreversibly with cysteines have reemerged as potent and selective tools for altering protein function, serving as chemical probes and even clinically approved drugs. The exquisite sensitivity of human immune cell signaling pathways to oxidative stress indicates the likely, yet still underexploited, general utility of covalent probes for selective chemical immunomodulation. Here, we provide an overview of immunomodulatory cysteines, including identification of electrophilic compounds available to label these residues. We focus our discussion on three protein classes essential for cell signaling, which span the 'druggability' spectrum from amenable to chemical probes (kinases), somewhat druggable (proteases), to inaccessible (phosphatases). Using existing inhibitors as a guide, we identify general strategies to guide the development of covalent probes for selected undruggable classes of proteins and propose the application of such compounds to alter immune cell functions.","is_dataset_classified":null,"base_score":3.091042453358316,"endowment":3.091042453358316,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"31204229","pmcid":null,"openalex_id":"https://openalex.org/W2949435945","authors":[],"funders":[{"funder_name":"David Geffen School of Medicine","grant_id":"","title":null},{"funder_name":"UCLA","grant_id":"","title":null},{"funder_name":"UCLA Jonsson Comprehensive Cancer Center","grant_id":"","title":null}],"total_grants":3,"fwci":1.106,"citation_percentile":0.72919632,"influential_citations":0,"citation_trend":[{"year":2019,"count":4},{"year":2020,"count":4},{"year":2021,"count":1},{"year":2022,"count":2},{"year":2023,"count":4},{"year":2024,"count":2},{"year":2025,"count":3},{"year":2026,"count":1}],"oa_status":"closed","license":"https://www.elsevier.com/legal/tdmrep-license","oa_locations":[{"url":"https://api.elsevier.com/content/article/PII:S0968089619302226?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0968089619302226?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.bmc.2019.05.050","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/31204229","host_type":"repository"}],"fields_of_study":["Click Chemistry and Applications","Peptidase Inhibition and Analysis","Adenosine and Purinergic Signaling","Cysteine","Enzyme Inhibitors","Humans","Immunologic Factors","Molecular Structure","Peptide Hydrolases","Phosphoric Monoester Hydrolases","Phosphotransferases","Signal Transduction"],"mesh_terms":["Cysteine","Enzyme Inhibitors","Humans","Immunologic Factors","Peptide Hydrolases","Phosphoric Monoester Hydrolases","Phosphotransferases","Molecular Structure","Signal Transduction"],"keywords":["Druggability","Chemistry","Chemical biology","Covalent bond","Proteases","Biochemistry","Drug discovery","Computational biology","Kinase","Chemical genetics","Signal transduction","Small molecule","Enzyme","Biology","Protease inhibitors","Chemical Immunology","Electrophiles","Kinase Inhibitors","Cysteines","Chemoproteomics","Covalent Inhibitors","Phosphatase Inhibitors","Covalent Immunomodulators"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-12T00:57:59.152421Z","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":[]}