{"doi":"10.3390/md19010041","title":"Topsentinol L Trisulfate, a Marine Natural Product That Targets Basal-like and Claudin-Low Breast Cancers","abstract":"Patients diagnosed with basal-like breast cancer suffer from poor prognosis and limited treatment options. There is an urgent need to identify new targets that can benefit patients with basal-like and claudin-low (BL-CL) breast cancers. We screened fractions from our Marine Invertebrate Compound Library (MICL) to identify compounds that specifically target BL-CL breast cancers. We identified a previously unreported trisulfated sterol, i.e., topsentinol L trisulfate (TLT), which exhibited increased efficacy against BL-CL breast cancers relative to luminal/HER2+ breast cancer. Biochemical investigation of the effects of TLT on BL-CL cell lines revealed its ability to inhibit activation of AMP-activated protein kinase (AMPK) and checkpoint kinase 1 (CHK1) and to promote activation of p38. The importance of targeting AMPK and CHK1 in BL-CL cell lines was validated by treating a panel of breast cancer cell lines with known small molecule inhibitors of AMPK (dorsomorphin) and CHK1 (Ly2603618) and recording the increased effectiveness against BL-CL breast cancers as compared with luminal/HER2+ breast cancer. Finally, we generated a drug response gene-expression signature and projected it against a human tumor panel of 12 different cancer types to identify other cancer types sensitive to the compound. The TLT sensitivity gene-expression signature identified breast and bladder cancer as the most sensitive to TLT, while glioblastoma multiforme was the least sensitive.","journal":"Marine Drugs","year":2021,"id":208115,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9408,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":38273,"name":"Thomas E. Smith","orcid":"0000-0002-4031-7753","position":1,"is_corresponding":false},{"id":566453,"name":"Gajendra Shrestha","orcid":"0000-0001-6525-7913","position":2,"is_corresponding":false},{"id":489778,"name":"Stephen Piccolo","orcid":"0000-0003-2001-5640","position":3,"is_corresponding":false},{"id":580974,"name":"Mary Kay Harper","orcid":null,"position":4,"is_corresponding":false},{"id":580975,"name":"Ryan M. Van Wagoner","orcid":null,"position":5,"is_corresponding":false},{"id":580623,"name":"Zhenyu Lu","orcid":"0000-0003-0420-437X","position":6,"is_corresponding":false},{"id":580976,"name":"Ashlee R. Venancio","orcid":null,"position":7,"is_corresponding":false},{"id":580624,"name":"Chris M. Ireland","orcid":"0009-0002-4079-1567","position":8,"is_corresponding":false},{"id":449639,"name":"Andrea H. Bild","orcid":"0000-0001-7906-6675","position":9,"is_corresponding":false},{"id":393343,"name":"Philip J. Moos","orcid":"0000-0002-8223-442X","position":10,"is_corresponding":false},{"id":580973,"name":"Nader N. El-Chaar","orcid":null,"position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-18T23:51:53.662668Z","pmid":"33477536","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":[]}