{"doi":"10.4049/jimmunol.163.10.5617","title":"The Antiinflammatory Sesquiterpene Lactone Parthenolide Inhibits NF-κB by Targeting the IκB Kinase Complex","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>The transcription factor NF-κB is a key regulator of the cellular inflammatory and immune response. Therefore, components of the NF-κB-activating signaling pathways are frequent targets for antiinflammatory agents. This study shows that the sesquiterpene lactone parthenolide inhibits a common step in NF-κB activation by preventing the TNF-α-induced induction of IκB kinase (IKK) and IKKβ, without affecting the activation of p38 and c-Jun N-terminal kinase. Parthenolide impairs NF-κB-dependent transcription triggered by expression of TNFR-associated factor-2, mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEKK1), and NF-κB-inducing kinase. This compound also prevents activation of both IKKs and DNA binding of NF-κB induced by MEKK and NF-κB-inducing kinase. Parthenolide targets a component of the IκB kinase complex without directly inhibiting IKKα, IKKβ, or MEKK1. Therefore, this sesquiterpene lactone could serve as a lead compound for the development of antiinflammatory remedies and is suitable as a molecular tool, allowing the dissection of TNF-α-derived signaling pathways leading to the activation of NF-κB, c-Jun N-terminal kinase, and p38.</jats:p>","journal":"The Journal of Immunology","year":1999,"id":596619,"datarank":0.881660367266946,"base_score":5.877735781779639,"endowment":5.877735781779639,"self_citation_contribution":0.881660367266946,"citation_network_contribution":0.0,"self_endowment_contribution":0.881660367266946,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":356,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"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":1528041,"name":"Thomas G Hofmann","orcid":null,"position":1,"is_corresponding":false},{"id":1528042,"name":"Wulf Dröge","orcid":null,"position":2,"is_corresponding":false},{"id":1528043,"name":"M Lienhard Schmitz","orcid":null,"position":3,"is_corresponding":false},{"id":1528039,"name":"Steffen P Hehner","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"The Antiinflammatory Sesquiterpene Lactone Parthenolide Inhibits NF-κB by Targeting the IκB Kinase Complex","abstract":"Abstract The transcription factor NF-κB is a key regulator of the cellular inflammatory and immune response. Therefore, components of the NF-κB-activating signaling pathways are frequent targets for antiinflammatory agents. This study shows that the sesquiterpene lactone parthenolide inhibits a common step in NF-κB activation by preventing the TNF-α-induced induction of IκB kinase (IKK) and IKKβ, without affecting the activation of p38 and c-Jun N-terminal kinase. Parthenolide impairs NF-κB-dependent transcription triggered by expression of TNFR-associated factor-2, mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEKK1), and NF-κB-inducing kinase. This compound also prevents activation of both IKKs and DNA binding of NF-κB induced by MEKK and NF-κB-inducing kinase. Parthenolide targets a component of the IκB kinase complex without directly inhibiting IKKα, IKKβ, or MEKK1. Therefore, this sesquiterpene lactone could serve as a lead compound for the development of antiinflammatory remedies and is suitable as a molecular tool, allowing the dissection of TNF-α-derived signaling pathways leading to the activation of NF-κB, c-Jun N-terminal kinase, and p38.","is_dataset_classified":null,"base_score":5.877735781779639,"endowment":5.877735781779639,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":null,"pmcid":null,"openalex_id":"https://openalex.org/W4313347901","authors":[],"funders":[],"total_grants":0,"fwci":3.5518,"citation_percentile":0.93285276,"influential_citations":0,"citation_trend":[{"year":2012,"count":10},{"year":2013,"count":20},{"year":2014,"count":10},{"year":2015,"count":8},{"year":2016,"count":9},{"year":2017,"count":10},{"year":2018,"count":18},{"year":2019,"count":11},{"year":2020,"count":6},{"year":2021,"count":10},{"year":2022,"count":7},{"year":2023,"count":8},{"year":2024,"count":8},{"year":2025,"count":9}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://journals.aai.org/jimmunol/article-pdf/163/10/5617/1104642/im229905617p.pdf","host_type":"journal"},{"url":"https://doi.org/10.4049/jimmunol.163.10.5617","host_type":"journal"}],"fields_of_study":["Sesquiterpenes and Asteraceae Studies","NF-κB Signaling Pathways","Natural product bioactivities and synthesis"],"mesh_terms":[],"keywords":["Parthenolide","IκB kinase","MAP kinase kinase kinase","Kinase","NF-κB","Sesquiterpene lactone","Cyclin-dependent kinase 9","Mitogen-activated protein kinase kinase","Signal transduction","Cell biology","Chemistry","Protein kinase A","Biology","Biochemistry","Sesquiterpene","Stereochemistry"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-28T10:47:39.030429Z","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":[]}