{"id":"https://openalex.org/W7223094734","doi":"https://doi.org/10.1021/acs.jmedchem.6c02682","title":"Structure-Based Design of 2-(Pyridone)Indoles as Antagonists of the Toll-Like Receptors TLR7 and TLR8 for the Treatment of Autoimmune Disorders","display_name":"Structure-Based Design of 2-(Pyridone)Indoles as Antagonists of the Toll-Like Receptors TLR7 and TLR8 for the Treatment of Autoimmune Disorders","publication_year":2026,"publication_date":"2026-10-21","ids":{"openalex":"https://openalex.org/W7223094734","doi":"https://doi.org/10.1021/acs.jmedchem.6c02682"},"language":"en","primary_location":{"id":"doi:10.1021/acs.jmedchem.6c02682","doi":"https://doi.org/10.1021/acs.jmedchem.6c02682","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jmedchem.6c02682","pdf_url":null,"source":{"id":"https://openalex.org/S162030435","display_name":"Journal of Medicinal Chemistry","issn_l":"0022-2623","issn":["0022-2623","1520-4804"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","jufo-3","ki-jl-2","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Medicinal Chemistry","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5090614281","display_name":"Dharmpal S. Dodd","orcid":"https://orcid.org/0009-0002-5515-7251","observed_orcids":["https://orcid.org/0009-0002-5515-7251"]},"institutions":[{"id":"https://openalex.org/I4210091812","display_name":"Bristol-Myers Squibb (United States)","ror":"https://ror.org/00gtmwv55","country_code":"US","type":"company","lineage":["https://openalex.org/I4210091812"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Dharmpal S. Dodd","raw_affiliation_strings":["Bristol Myers Squibb Research and Development , P.O. Box 4000, , ,"],"raw_orcid":"https://orcid.org/0009-0002-5515-7251","affiliations":[{"raw_affiliation_string":"Bristol Myers Squibb Research and Development , P.O. Box 4000, , ,","institution_ids":["https://openalex.org/I4210091812"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5068478314","display_name":"John L. Gilmore","orcid":"https://orcid.org/0000-0002-0520-8746","observed_orcids":["https://orcid.org/0000-0002-0520-8746"]},"institutions":[{"id":"https://openalex.org/I4210091812","display_name":"Bristol-Myers Squibb (United States)","ror":"https://ror.org/00gtmwv55","country_code":"US","type":"company","lineage":["https://openalex.org/I4210091812"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"John L. Gilmore","raw_affiliation_strings":["Bristol Myers Squibb Research and Development , P.O. Box 4000, , ,"],"raw_orcid":"https://orcid.org/0000-0002-0520-8746","affiliations":[{"raw_affiliation_string":"Bristol Myers Squibb Research and Development , P.O. Box 4000, , ,","institution_ids":["https://openalex.org/I4210091812"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5016987738","display_name":"Tasir S. Haque","orcid":"https://orcid.org/0009-0006-2274-8492","observed_orcids":["https://orcid.org/0009-0006-2274-8492"]},"institutions":[{"id":"https://openalex.org/I4210091812","display_name":"Bristol-Myers Squibb (United States)","ror":"https://ror.org/00gtmwv55","country_code":"US","type":"company","lineage":["https://openalex.org/I4210091812"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Tasir S. Haque","raw_affiliation_strings":["Bristol Myers Squibb Research and Development , P.O. Box 4000, , ,"],"raw_orcid":"https://orcid.org/0009-0006-2274-8492","affiliations":[{"raw_affiliation_string":"Bristol Myers Squibb Research and Development , P.O. Box 4000, , ,","institution_ids":["https://openalex.org/I4210091812"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5159221063","display_name":"Brian K. Whiteley","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210091812","display_name":"Bristol-Myers Squibb (United States)","ror":"https://ror.org/00gtmwv55","country_code":"US","type":"company","lineage":["https://openalex.org/I4210091812"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Brian K. Whiteley","raw_affiliation_strings":["Bristol Myers Squibb Research and Development , P.O. Box 4000, , ,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Bristol Myers Squibb Research and Development , P.O. Box 4000, , ,","institution_ids":["https://openalex.org/I4210091812"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5055669862","display_name":"Shana Posy","orcid":"https://orcid.org/0000-0001-9298-899X","observed_orcids":["https://orcid.org/0000-0001-9298-899X"]},"institutions":[{"id":"https://openalex.org/I4210091812","display_name":"Bristol-Myers Squibb (United States)","ror":"https://ror.org/00gtmwv55","country_code":"US","type":"company","lineage":["https://openalex.org/I4210091812"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Shana L. Posy","raw_affiliation_strings":["Bristol Myers Squibb Research and Development , P.O. Box 4000, , ,"],"raw_orcid":"https://orcid.org/0000-0001-9298-899X","affiliations":[{"raw_affiliation_string":"Bristol Myers Squibb Research and Development , P.O. Box 4000, , ,","institution_ids":["https://openalex.org/I4210091812"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5045994479","display_name":"Dawn Mulligan","orcid":"https://orcid.org/0009-0006-7578-530X","observed_orcids":["https://orcid.org/0009-0006-7578-530X"]},"institutions":[{"id":"https://openalex.org/I4210091812","display_name":"Bristol-Myers Squibb (United States)","ror":"https://ror.org/00gtmwv55","country_code":"US","type":"company","lineage":["https://openalex.org/I4210091812"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Dawn Mulligan","raw_affiliation_strings":["Bristol Myers Squibb Research and Development , P.O. Box 4000, , ,"],"raw_orcid":"https://orcid.org/0009-0006-7578-530X","affiliations":[{"raw_affiliation_string":"Bristol Myers Squibb Research and Development , P.O. Box 4000, , ,","institution_ids":["https://openalex.org/I4210091812"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5016607794","display_name":"David Critton","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210091812","display_name":"Bristol-Myers Squibb (United States)","ror":"https://ror.org/00gtmwv55","country_code":"US","type":"company","lineage":["https://openalex.org/I4210091812"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"David Critton","raw_affiliation_strings":["Bristol Myers Squibb Research and Development , P.O. Box 4000, , ,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Bristol Myers Squibb Research and Development , P.O. Box 4000, , ,","institution_ids":["https://openalex.org/I4210091812"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5087132511","display_name":"Rosemary Zhang","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210091812","display_name":"Bristol-Myers Squibb (United States)","ror":"https://ror.org/00gtmwv55","country_code":"US","type":"company","lineage":["https://openalex.org/I4210091812"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Rosemary Zhang","raw_affiliation_strings":["Bristol Myers Squibb Research and Development , P.O. Box 4000, , ,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Bristol Myers Squibb Research and Development , P.O. Box 4000, , ,","institution_ids":["https://openalex.org/I4210091812"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5109232320","display_name":"Hongchen Qiu","orcid":"https://orcid.org/0009-0006-0187-1088","observed_orcids":["https://orcid.org/0009-0006-0187-1088"]},"institutions":[{"id":"https://openalex.org/I4210091812","display_name":"Bristol-Myers Squibb (United States)","ror":"https://ror.org/00gtmwv55","country_code":"US","type":"company","lineage":["https://openalex.org/I4210091812"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Hongchen Qiu","raw_affiliation_strings":["Bristol Myers Squibb Research and Development , P.O. Box 4000, , ,"],"raw_orcid":"https://orcid.org/0009-0006-0187-1088","affiliations":[{"raw_affiliation_string":"Bristol Myers Squibb Research and Development , P.O. Box 4000, , ,","institution_ids":["https://openalex.org/I4210091812"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5073504315","display_name":"Mary Ellen Cvijic","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210091812","display_name":"Bristol-Myers Squibb (United States)","ror":"https://ror.org/00gtmwv55","country_code":"US","type":"company","lineage":["https://openalex.org/I4210091812"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Mary Ellen Cvijic","raw_affiliation_strings":["Bristol Myers Squibb Research and Development , P.O. Box 4000, , ,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Bristol Myers Squibb Research and Development , P.O. Box 4000, , ,","institution_ids":["https://openalex.org/I4210091812"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5111201384","display_name":"Murali Subramanian","orcid":"https://orcid.org/0009-0001-9742-7961","observed_orcids":["https://orcid.org/0009-0001-9742-7961"]},"institutions":[{"id":"https://openalex.org/I4210091812","display_name":"Bristol-Myers Squibb (United States)","ror":"https://ror.org/00gtmwv55","country_code":"US","type":"company","lineage":["https://openalex.org/I4210091812"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Murali Subramanian","raw_affiliation_strings":["The Biocon Bristol Myers Squibb Research & Development Center , ,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"The Biocon Bristol Myers Squibb Research & Development Center , ,","institution_ids":["https://openalex.org/I4210091812"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5077794783","display_name":"Debarati Mazumder Tagore","orcid":"https://orcid.org/0000-0002-4100-2905","observed_orcids":["https://orcid.org/0000-0002-4100-2905"]},"institutions":[{"id":"https://openalex.org/I4210091812","display_name":"Bristol-Myers Squibb (United States)","ror":"https://ror.org/00gtmwv55","country_code":"US","type":"company","lineage":["https://openalex.org/I4210091812"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Debarati Mazumder Tagore","raw_affiliation_strings":["The Biocon Bristol Myers Squibb Research & Development Center , ,"],"raw_orcid":"https://orcid.org/0000-0002-4100-2905","affiliations":[{"raw_affiliation_string":"The Biocon Bristol Myers Squibb Research & Development Center , ,","institution_ids":["https://openalex.org/I4210091812"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5010115884","display_name":"Shailesh P. Dudhgaonkar","orcid":"https://orcid.org/0000-0003-1694-3460","observed_orcids":["https://orcid.org/0000-0003-1694-3460"]},"institutions":[{"id":"https://openalex.org/I4210091812","display_name":"Bristol-Myers Squibb (United States)","ror":"https://ror.org/00gtmwv55","country_code":"US","type":"company","lineage":["https://openalex.org/I4210091812"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Shailesh Dudhgaonkar","raw_affiliation_strings":["The Biocon Bristol Myers Squibb Research & Development Center , ,"],"raw_orcid":"https://orcid.org/0000-0003-1694-3460","affiliations":[{"raw_affiliation_string":"The Biocon Bristol Myers Squibb Research & Development Center , ,","institution_ids":["https://openalex.org/I4210091812"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5029498356","display_name":"Mary J. Harner","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210091812","display_name":"Bristol-Myers Squibb (United States)","ror":"https://ror.org/00gtmwv55","country_code":"US","type":"company","lineage":["https://openalex.org/I4210091812"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Mary Harner","raw_affiliation_strings":["Bristol Myers Squibb Research and Development , P.O. Box 4000, , ,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Bristol Myers Squibb Research and Development , P.O. Box 4000, , ,","institution_ids":["https://openalex.org/I4210091812"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5084550335","display_name":"Louis J. Lombardo","orcid":"https://orcid.org/0000-0003-3335-6460","observed_orcids":["https://orcid.org/0000-0003-3335-6460"]},"institutions":[{"id":"https://openalex.org/I4210091812","display_name":"Bristol-Myers Squibb (United States)","ror":"https://ror.org/00gtmwv55","country_code":"US","type":"company","lineage":["https://openalex.org/I4210091812"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Louis J. Lombardo","raw_affiliation_strings":["Bristol Myers Squibb Research and Development , P.O. Box 4000, , ,"],"raw_orcid":"https://orcid.org/0000-0003-3335-6460","affiliations":[{"raw_affiliation_string":"Bristol Myers Squibb Research and Development , P.O. Box 4000, , ,","institution_ids":["https://openalex.org/I4210091812"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5070894857","display_name":"John E. Macor","orcid":"https://orcid.org/0009-0000-9040-5770","observed_orcids":["https://orcid.org/0009-0000-9040-5770"]},"institutions":[{"id":"https://openalex.org/I4210091812","display_name":"Bristol-Myers Squibb (United States)","ror":"https://ror.org/00gtmwv55","country_code":"US","type":"company","lineage":["https://openalex.org/I4210091812"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"John E. Macor","raw_affiliation_strings":["Bristol Myers Squibb Research and Development , P.O. Box 4000, , ,"],"raw_orcid":"https://orcid.org/0009-0000-9040-5770","affiliations":[{"raw_affiliation_string":"Bristol Myers Squibb Research and Development , P.O. Box 4000, , ,","institution_ids":["https://openalex.org/I4210091812"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5048703920","display_name":"Stefan U. Ruepp","orcid":"https://orcid.org/0009-0008-7476-7614","observed_orcids":["https://orcid.org/0009-0008-7476-7614"]},"institutions":[{"id":"https://openalex.org/I4210091812","display_name":"Bristol-Myers Squibb (United States)","ror":"https://ror.org/00gtmwv55","country_code":"US","type":"company","lineage":["https://openalex.org/I4210091812"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Stefan Ruepp","raw_affiliation_strings":["Bristol Myers Squibb Research and Development , P.O. Box 4000, , ,"],"raw_orcid":"https://orcid.org/0009-0008-7476-7614","affiliations":[{"raw_affiliation_string":"Bristol Myers Squibb Research and Development , P.O. Box 4000, , ,","institution_ids":["https://openalex.org/I4210091812"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5060371965","display_name":"Gary L. Schieven","orcid":"https://orcid.org/0009-0004-4830-9020","observed_orcids":["https://orcid.org/0009-0004-4830-9020"]},"institutions":[{"id":"https://openalex.org/I4210091812","display_name":"Bristol-Myers Squibb (United States)","ror":"https://ror.org/00gtmwv55","country_code":"US","type":"company","lineage":["https://openalex.org/I4210091812"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Gary L. Schieven","raw_affiliation_strings":["Bristol Myers Squibb Research and Development , P.O. Box 4000, , ,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Bristol Myers Squibb Research and Development , P.O. Box 4000, , ,","institution_ids":["https://openalex.org/I4210091812"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5053704764","display_name":"Alaric J. Dyckman","orcid":"https://orcid.org/0000-0002-1050-2077","observed_orcids":["https://orcid.org/0000-0002-1050-2077"]},"institutions":[{"id":"https://openalex.org/I4210091812","display_name":"Bristol-Myers Squibb (United States)","ror":"https://ror.org/00gtmwv55","country_code":"US","type":"company","lineage":["https://openalex.org/I4210091812"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Alaric J. Dyckman","raw_affiliation_strings":["Bristol Myers Squibb Research and Development , P.O. Box 4000, , ,"],"raw_orcid":"https://orcid.org/0000-0002-1050-2077","affiliations":[{"raw_affiliation_string":"Bristol Myers Squibb Research and Development , P.O. Box 4000, , ,","institution_ids":["https://openalex.org/I4210091812"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5053704764"],"corresponding_institution_ids":["https://openalex.org/I4210091812"],"apc_list":{"value":4500,"currency":"USD","value_usd":4500},"apc_paid":null,"fwci":0.0,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":{"value":0.75209982,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10371","display_name":"Immune Response and Inflammation","score":0.8539999723434448,"subfield":{"id":"https://openalex.org/subfields/2403","display_name":"Immunology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10371","display_name":"Immune Response and Inflammation","score":0.8539999723434448,"subfield":{"id":"https://openalex.org/subfields/2403","display_name":"Immunology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10211","display_name":"Computational Drug Discovery Methods","score":0.07169999927282333,"subfield":{"id":"https://openalex.org/subfields/1703","display_name":"Computational Theory and Mathematics"},"field":{"id":"https://openalex.org/fields/17","display_name":"Computer Science"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T10274","display_name":"Heterocyclic Compound Synthesis and Bioactivity","score":0.01640000008046627,"subfield":{"id":"https://openalex.org/subfields/1605","display_name":"Organic Chemistry"},"field":{"id":"https://openalex.org/fields/16","display_name":"Chemistry"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/tlr7","display_name":"TLR7","score":0.796999990940094},{"id":"https://openalex.org/keywords/tlr8","display_name":"TLR8","score":1.0},{"id":"https://openalex.org/keywords/structure-based-drug-design","display_name":"structure-based drug design","score":0.9150000214576721},{"id":"https://openalex.org/keywords/autoimmune-disease","display_name":"autoimmune disease","score":0.777999997138977},{"id":"https://openalex.org/keywords/lupus","display_name":"lupus","score":0.8809999823570251},{"id":"https://openalex.org/keywords/antiproliferative-activity","display_name":"antiproliferative activity","score":0.8989999890327454},{"id":"https://openalex.org/keywords/interleukin-6","display_name":"interleukin-6","score":0.6520000100135803},{"id":"https://openalex.org/keywords/interferon-alpha","display_name":"interferon-alpha","score":0.8600000143051147},{"id":"https://openalex.org/keywords/oral-bioavailability","display_name":"oral bioavailability","score":0.8640000224113464},{"id":"https://openalex.org/keywords/pharmacodynamic-modeling","display_name":"pharmacodynamic modeling","score":0.4390000104904175},{"id":"https://openalex.org/keywords/innate-immunity","display_name":"innate immunity","score":0.5170000195503235}],"concepts":[{"id":"https://openalex.org/C2779836521","wikidata":"https://www.wikidata.org/wiki/Q14914081","display_name":"TLR7","level":5,"score":0.7402999997138977},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.7178999781608582},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.6488999724388123},{"id":"https://openalex.org/C170493617","wikidata":"https://www.wikidata.org/wiki/Q208467","display_name":"Receptor","level":2,"score":0.5823000073432922},{"id":"https://openalex.org/C16613235","wikidata":"https://www.wikidata.org/wiki/Q285982","display_name":"Endogeny","level":2,"score":0.5618000030517578},{"id":"https://openalex.org/C8891405","wikidata":"https://www.wikidata.org/wiki/Q1059","display_name":"Immune system","level":2,"score":0.5479999780654907},{"id":"https://openalex.org/C111113717","wikidata":"https://www.wikidata.org/wiki/Q725307","display_name":"Pharmacodynamics","level":3,"score":0.41940000653266907},{"id":"https://openalex.org/C181389837","wikidata":"https://www.wikidata.org/wiki/Q461809","display_name":"Bioavailability","level":2,"score":0.4016000032424927},{"id":"https://openalex.org/C136449434","wikidata":"https://www.wikidata.org/wiki/Q428253","display_name":"Innate immune system","level":3,"score":0.3598000109195709},{"id":"https://openalex.org/C2779075594","wikidata":"https://www.wikidata.org/wiki/Q8084905","display_name":"Autoimmune disease","level":3,"score":0.35019999742507935},{"id":"https://openalex.org/C1491633281","wikidata":"https://www.wikidata.org/wiki/Q7868","display_name":"Cell","level":2,"score":0.3398999869823456},{"id":"https://openalex.org/C202751555","wikidata":"https://www.wikidata.org/wiki/Q221681","display_name":"In vitro","level":2,"score":0.33970001339912415},{"id":"https://openalex.org/C2776914184","wikidata":"https://www.wikidata.org/wiki/Q101991","display_name":"Inflammation","level":2,"score":0.3264000117778778},{"id":"https://openalex.org/C2777752497","wikidata":"https://www.wikidata.org/wiki/Q286779","display_name":"IC50","level":3,"score":0.3034000098705292},{"id":"https://openalex.org/C110121322","wikidata":"https://www.wikidata.org/wiki/Q865811","display_name":"Distribution (mathematics)","level":2,"score":0.301800012588501},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.29010000824928284},{"id":"https://openalex.org/C207001950","wikidata":"https://www.wikidata.org/wiki/Q141124","display_name":"In vivo","level":2,"score":0.28380000591278076},{"id":"https://openalex.org/C67705224","wikidata":"https://www.wikidata.org/wiki/Q11053","display_name":"RNA","level":3,"score":0.2599000036716461},{"id":"https://openalex.org/C2776090121","wikidata":"https://www.wikidata.org/wiki/Q193529","display_name":"T cell","level":3,"score":0.2549000084400177}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1021/acs.jmedchem.6c02682","doi":"https://doi.org/10.1021/acs.jmedchem.6c02682","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jmedchem.6c02682","pdf_url":null,"source":{"id":"https://openalex.org/S162030435","display_name":"Journal of Medicinal Chemistry","issn_l":"0022-2623","issn":["0022-2623","1520-4804"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","jufo-3","ki-jl-2","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Medicinal Chemistry","raw_type":"journal-article"}],"best_oa_location":null,"sustainable_development_goals":[{"score":0.9763000011444092,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":26,"referenced_works":["https://openalex.org/W1542562771","https://openalex.org/W1542775986","https://openalex.org/W1965777226","https://openalex.org/W1969072247","https://openalex.org/W1995586746","https://openalex.org/W2008680676","https://openalex.org/W2013708530","https://openalex.org/W2040213563","https://openalex.org/W2041535798","https://openalex.org/W2042433863","https://openalex.org/W2061343703","https://openalex.org/W2062267695","https://openalex.org/W2069394593","https://openalex.org/W2071301649","https://openalex.org/W2109491705","https://openalex.org/W2346299902","https://openalex.org/W2413339906","https://openalex.org/W2605100179","https://openalex.org/W2771435967","https://openalex.org/W3000211595","https://openalex.org/W3012283572","https://openalex.org/W3046159581","https://openalex.org/W3046455346","https://openalex.org/W4280575746","https://openalex.org/W7129342677","https://openalex.org/W7165113598"],"related_works":["https://openalex.org/W4280575746","https://openalex.org/W3046455346","https://openalex.org/W4220824457","https://openalex.org/W7161360340","https://openalex.org/W7130317055","https://openalex.org/W7170065717","https://openalex.org/W4292073241","https://openalex.org/W2890635129","https://openalex.org/W3037156656","https://openalex.org/W2986477867"],"abstract_inverted_index":{"Abstract":[0],"Toll-like":[1],"receptors":[2],"7":[3],"and":[4,26,34,57,99,121,126,137],"8":[5],"(TLR7/8)":[6],"are":[7],"innate":[8],"immune":[9,77],"sensors":[10],"whose":[11],"activation":[12],"by":[13],"endogenous":[14],"RNA":[15],"ligands":[16],"is":[17],"a":[18,74,141],"hallmark":[19],"of":[20,36,60,76,96,100,119],"chronic":[21],"autoimmune":[22],"disorders,":[23],"notably":[24],"cutaneous":[25],"systemic":[27],"lupus.":[28],"We":[29],"present":[30],"the":[31],"structure-based":[32],"design":[33],"optimization":[35,80],"2-(pyridin-2(1H)-one)indoles":[37],"as":[38],"potent":[39,93],"dual":[40],"TLR7/8":[41],"antagonists":[42,94],"with":[43,114],"properties":[44],"improved":[45],"over":[46],"our":[47],"prior":[48],"series,":[49],"including":[50],"increased":[51],"permeability,":[52],"reduced":[53,58],"ion":[54],"channel":[55],"activity,":[56],"volume":[59],"distribution":[61],"at":[62],"steady":[63],"state":[64],"(Vss).":[65],"Initial":[66],"pyridone":[67],"leads":[68],"displayed":[69],"unexpected":[70],"anti-proliferative":[71,101],"activity":[72],"in":[73,110,140],"panel":[75],"cell":[78],"lines;":[79],"against":[81,124],"an":[82],"identified":[83],"off-target":[84],"BRD4":[85,97],"liability,":[86],"hypothesized":[87],"to":[88],"drive":[89],"this":[90],"effect,":[91],"delivered":[92],"devoid":[95],"binding":[98],"activity.":[102],"These":[103],"compounds":[104],"potently":[105],"inhibited":[106],"TLR7/8-mediated":[107],"IL-6":[108,136],"production":[109],"human":[111],"whole":[112],"blood,":[113],"9a":[115],"giving":[116],"IC50":[117],"values":[118],"9.4":[120],"1.3":[122],"nM":[123],"TLR7":[125],"TLR8,":[127],"respectively.":[128],"This":[129],"orally":[130],"bioavailable":[131],"lead":[132],"dose-dependently":[133],"suppressed":[134],"TLR7-mediated":[135],"IFN\u03b1":[138],"release":[139],"mouse":[142],"pharmacodynamic":[143],"model.":[144]},"counts_by_year":[],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2026-10-22T00:00:00"}
