{"doi":"10.1002/cmdc.202400418","title":"The Investigation of Hsp90C‐Terminal Inhibitors Containing Amide Bioisosteres","abstract":"Abstract Heat Shock Protein 90 (Hsp90) is responsible for the proper folding and maturation of ~400 client protein substrates, many of which are directly associated with the ten hallmarks of cancer. Hsp90 is a great target for cancer therapy including melanoma, since Hsp90 inhibition can disrupt multiple oncogenic pathways simultaneously. In this study, we report the synthesis and anti‐proliferative activity manifested by a series of Hsp90 C‐terminal inhibitors against mutant BRAF and wild‐type BRAF melanoma cells. Furthermore, we explored structure‐activity relationships (SAR) for the amide moiety of 6 ( B1 ), a novel Hsp90C‐terminal inhibitor via introduction of amide bioisosteres. Compound 6 displayed an IC 50 of 1.01 μM, 0.782 μM, 0.607 μM and 1.413 μM against SKMel173, SKMel103, SKMel19 and A375 cells, respectively.","journal":"ChemMedChem","year":2024,"id":452295,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9566,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":402500,"name":"Chitra Subramanian","orcid":"0000-0003-1871-2834","position":1,"is_corresponding":false},{"id":1274525,"name":"Reagan Long","orcid":null,"position":2,"is_corresponding":false},{"id":1254387,"name":"Kelli McNamara","orcid":null,"position":3,"is_corresponding":false},{"id":402505,"name":"Mark S. Cohen","orcid":"0000-0002-2517-0757","position":4,"is_corresponding":false},{"id":288121,"name":"Brian S. J. Blagg","orcid":"0000-0002-6200-3480","position":5,"is_corresponding":false},{"id":872515,"name":"Eva Amatya","orcid":"0000-0001-5494-3256","position":0,"is_corresponding":true}],"reference_count":26,"raw_metadata":null,"created_at":"2026-07-19T02:02:50.407779Z","pmid":"39153203","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":[]}