{"entity": "journal", "iuid": "1306a8f05dd649ea826bdec2277ba544", "timestamp": "2026-09-05T13:47:04.335Z", "links": {"self": {"href": "https://publications.scilifelab.se/journal/Biochem.%20Pharmacol..json"}, "display": {"href": "https://publications.scilifelab.se/journal/Biochem.%20Pharmacol."}}, "title": "Biochem. Pharmacol.", "issn": "1873-2968", "issn-l": "0006-2952", "publications_count": 2, "publications": [{"entity": "publication", "iuid": "629f4e33d2904b008c9dec10e46bbed6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/629f4e33d2904b008c9dec10e46bbed6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/629f4e33d2904b008c9dec10e46bbed6"}}, "title": "Albacarcin V adds EPLIN as a novel and promising target for the treatment of female cancers and pediatric medulloblastoma.", "authors": [{"family": "Krahulcov\u00e1", "given": "Lucia", "initials": "L"}, {"family": "Lindell", "given": "Emma", "initials": "E"}, {"family": "Lu", "given": "Xi", "initials": "X"}, {"family": "Conejeros Monsalve", "given": "Jessica Javiera", "initials": "JJ"}, {"family": "Haraldsson", "given": "Martin", "initials": "M"}, {"family": "Li", "given": "Zhixiong", "initials": "Z"}, {"family": "Chen", "given": "Xinsong", "initials": "X"}, {"family": "Aune", "given": "Guro", "initials": "G"}, {"family": "Zhao", "given": "Miao", "initials": "M"}, {"family": "Tong", "given": "Le", "initials": "L"}, {"family": "Hartman", "given": "Johan", "initials": "J"}, {"family": "Lehti", "given": "Kaisa", "initials": "K"}, {"family": "Swartling", "given": "Fredrik Johansson", "initials": "FJ"}, {"family": "Chen", "given": "Xingqi", "initials": "X"}, {"family": "Sj\u00f6blom", "given": "Tobias", "initials": "T"}, {"family": "Zhang", "given": "Xiaonan", "initials": "X"}], "type": "journal article", "published": "2026-02-00", "journal": {"title": "Biochem. Pharmacol.", "issn": "1873-2968", "issn-l": "0006-2952", "volume": "244", "issue": null, "pages": "117625"}, "abstract": "Breast and ovarian cancers remain among the most lethal malignancies affecting women worldwide. Despite advances in standard therapies, drug resistance and high relapse rates continue to undermine long-term treatment outcomes. To address these challenges, we re-evaluated five previously identified drug candidates (FLIX1-FLIX5), all of which are effective at nanomolar concentrations in breast and ovarian cancer cell lines. Among them, FLIX3 (Albacarcin V) and FLIX4 exhibited the most potent cytotoxicity, with IC50 values below 50 nM across multiple cell lines. Notably, FLIX3 also exhibited nanomolar-range efficacy in drug-resistant, patient-derived samples from triple-negative breast cancer (TNBC) and ovarian cancer. In a zebrafish model, FLIX3 effectively eliminated cancer cells within its safety window. ATAC-Seq analysis revealed that both compounds induce significant epigenetic alterations. Proteome Integral Solubility Alteration (PISA) and cellular thermal shift assay (CETSA) identified EPLIN (Epithelial Protein Lost in Neoplasm) as the top target of FLIX3 but not FLIX4. EPLIN was previously identified as the primary target of FLIX5. Its re-emergence as the dominant target of FLIX3 highlights its potential as a broadly applicable therapeutic target. Collectively, these findings support the continued development of EPLIN-targeting compounds as promising agents for treating aggressive and drug-resistant breast and ovarian cancers.", "doi": "10.1016/j.bcp.2025.117625", "pmid": "41360228", "labels": {"Chemical Biology Consortium Sweden": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S0006-2952(25)00890-1"}], "notes": [], "created": "2026-07-01T07:44:06.836Z", "modified": "2026-07-01T07:45:51.888Z"}, {"entity": "publication", "iuid": "654029ff29274b27bc5f4a687bf8d376", "links": {"self": {"href": "https://publications.scilifelab.se/publication/654029ff29274b27bc5f4a687bf8d376.json"}, "display": {"href": "https://publications.scilifelab.se/publication/654029ff29274b27bc5f4a687bf8d376"}}, "title": "Esomeprazole reduces sperm motility index by targeting the spermic cholinergic machinery: A mechanistic study for the association between use of proton pump inhibitors and reduced sperm motility index.", "authors": [{"family": "Kumar", "given": "Amit", "initials": "A"}, {"family": "Kumar", "given": "Rajnish", "initials": "R"}, {"family": "Flanagan", "given": "John", "initials": "J"}, {"family": "L\u00e5ngstr\u00f6m", "given": "Bengt", "initials": "B"}, {"family": "Bj\u00f6rndahl", "given": "Lars", "initials": "L"}, {"family": "Darreh-Shori", "given": "Taher", "initials": "T"}], "type": "journal article", "published": "2020-12-00", "journal": {"title": "Biochem. Pharmacol.", "issn": "1873-2968", "volume": "182", "pages": "114212", "issn-l": "0006-2952"}, "abstract": "Recent studies have linked prolonged use of the most commonly prescribed proton pump inhibitors (PPIs) with declined human sperm function and infertility. Here, we report for the first time the most plausible underlying mechanism for this unwarranted secondary mode of action. We followed up on a recent serendipitous discovery in our laboratory regarding PPIs' off-target action and performed detailed pharmacodynamic analyses by combining in silico and in vitro studies to determine the off-target effect of one of the most commonly used PPI, esomeprazole, on the key human acetylcholine biosynthesizing enzyme, choline acetyltransferase (ChAT; EC 2.3.1.6). A pivotal enzyme in the spermic cholinergic system that governs the sperm motility, concentration and quality. Our results were conclusive and showed that both the racemic form, omeprazole and its pure S-enantiomer, esomeprazole, acted as potent mixed-competitive inhibitor of human ChAT with a global inhibition constant (Ki) of 88 nM (95%CI: 10-167 nM) for esomeprazole and 178 nM (95%CI: 140-230 nM) for the racemic drug omeprazole. Most importantly, esomeprazole substantially reduces both total number of motile sperm (by 36%, p < 0.001; and 21% p < 0.0001, at 10 and 100 nM, respectively) as well as the total number of sperm with progressive motility (by 42% p < 0.0016 and by 26% p < 0.0001, respectively) after 60 min relative to 20 min incubation in our ex vivo functional assay performed on ejaculated human sperm. In conclusion, this study presents a completely new perspective regarding PPIs secondary mode of action/unwarranted side effects and calls for further mechanistic and larger clinical studies to elucidate the role of PPIs in infertility.", "doi": "10.1016/j.bcp.2020.114212", "pmid": "32866455", "labels": {"Protein Science Facility (PSF)": "Service"}, "xrefs": [{"db": "pii", "key": "S0006-2952(20)30448-2"}], "notes": [], "created": "2024-04-03T14:17:50.894Z", "modified": "2024-04-03T14:17:50.899Z"}], "created": "2020-01-23T13:18:32.421Z", "modified": "2020-11-27T13:14:07.518Z"}