{"doi":"10.3390/molecules28020677","title":"Carbohydrate-Small Molecule Hybrids as Lead Compounds Targeting IL-6 Signaling","abstract":"In the past 25 years, a number of efforts have been made toward the development of small molecule interleukin-6 (IL-6) signaling inhibitors, but none have been approved to date. Monosaccharides are a diverse class of bioactive compounds, but thus far have been unexplored as a scaffold for small molecule IL-6-signaling inhibitor design. Therefore, in this present communication, we combined a structure-based drug design approach with carbohydrate building blocks to design and synthesize novel IL-6-signaling inhibitors targeting glycoprotein 130 (gp130). Of this series of compounds, LS-TG-2P and LS-TF-3P were the top lead compounds, displaying IC50 values of 6.9 and 16 µM against SUM159 cell lines, respectively, while still retaining preferential activity against the IL-6-signaling pathway. The carbohydrate moiety was found to improve activity, as N-unsubstituted triazole analogues of these compounds were found to be less active in vitro compared to the leads themselves. Thus, LS-TG-2P and LS-TF-3P are promising scaffolds for further development and study as IL-6-signaling inhibitors.","journal":"Molecules","year":2023,"id":363381,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9547,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":748758,"name":"Li Pan","orcid":"0000-0003-3720-5504","position":1,"is_corresponding":false},{"id":660351,"name":"Tiffany Wang","orcid":"0000-0001-6444-4020","position":2,"is_corresponding":false},{"id":1117843,"name":"Conner Booker","orcid":null,"position":3,"is_corresponding":false},{"id":1117844,"name":"Iram Hyder","orcid":null,"position":4,"is_corresponding":false},{"id":1117401,"name":"Laura E. Hanold","orcid":"0000-0003-4492-9885","position":5,"is_corresponding":false},{"id":668260,"name":"Garret M. Rubin","orcid":"0000-0001-6750-7453","position":6,"is_corresponding":false},{"id":376199,"name":"Yousong Ding","orcid":"0000-0001-8610-0659","position":7,"is_corresponding":false},{"id":721018,"name":"Jiayuh Lin","orcid":"0000-0002-5618-8781","position":8,"is_corresponding":false},{"id":292728,"name":"Chenglong Li","orcid":"0000-0001-9460-3168","position":9,"is_corresponding":false},{"id":963526,"name":"Daniel Schultz","orcid":"0000-0002-7727-9148","position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-19T01:14:28.054440Z","pmid":"36677735","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":[]}