{"entity": "researcher", "timestamp": "2026-08-23T14:33:08.994Z", "family": "Fetzer", "given": "Christian", "initials": "C", "orcid": "0000-0001-5510-1544", "affiliations": ["Center for Integrated Protein Science at the Department of Chemistry, Technische Universit\u00e4t M\u00fcnchen, Garching bei M\u00fcnchen, Germany.", "Chair of Organic Chemistry II, Technische Universit\u00e4t M\u00fcnchen, Garching bei M\u00fcnchen, Germany."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/212fa3a1fe1047599ca742296cd974b8.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/212fa3a1fe1047599ca742296cd974b8"}}, "publications": [{"entity": "publication", "iuid": "3e82d78e3ce6427e8aade0e64c2abd11", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/3e82d78e3ce6427e8aade0e64c2abd11.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/3e82d78e3ce6427e8aade0e64c2abd11"}}, "title": "Repurposing human kinase inhibitors to create an antibiotic active against drug-resistant Staphylococcus aureus, persisters and biofilms.", "authors": [{"family": "Le", "given": "Philipp", "initials": "P"}, {"family": "Kunold", "given": "Elena", "initials": "E"}, {"family": "Macsics", "given": "Robert", "initials": "R"}, {"family": "Rox", "given": "Katharina", "initials": "K"}, {"family": "Jennings", "given": "Megan C", "initials": "MC"}, {"family": "Ugur", "given": "Ilke", "initials": "I"}, {"family": "Reinecke", "given": "Maria", "initials": "M"}, {"family": "Chaves-Moreno", "given": "Diego", "initials": "D"}, {"family": "Hackl", "given": "Mathias W", "initials": "MW", "orcid": "0000-0002-8380-4439", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5501e02c6b324709976134372451a6ef.json"}}, {"family": "Fetzer", "given": "Christian", "initials": "C", "orcid": "0000-0001-5510-1544", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/212fa3a1fe1047599ca742296cd974b8.json"}}, {"family": "Mandl", "given": "Franziska A M", "initials": "FAM"}, {"family": "Lehmann", "given": "Johannes", "initials": "J"}, {"family": "Korotkov", "given": "Vadim S", "initials": "VS", "orcid": "0000-0003-3970-2483", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/99f1fc62226b478a86ac5da5be09e39e.json"}}, {"family": "Hacker", "given": "Stephan M", "initials": "SM", "orcid": "0000-0001-5420-4824", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bdf56cd34ed241bc834a58a0f68b9d8d.json"}}, {"family": "Kuster", "given": "Bernhard", "initials": "B", "orcid": "0000-0002-9094-1677", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5196477f29b345ccb3f4a8fc32c9fac4.json"}}, {"family": "Antes", "given": "Iris", "initials": "I"}, {"family": "Pieper", "given": "Dietmar H", "initials": "DH"}, {"family": "Rohde", "given": "Manfred", "initials": "M"}, {"family": "Wuest", "given": "William M", "initials": "WM"}, {"family": "Medina", "given": "Eva", "initials": "E"}, {"family": "Sieber", "given": "Stephan A", "initials": "SA", "orcid": "0000-0002-9400-906X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ed221037cc8f4af18984505bc69cd193.json"}}], "type": "journal article", "published": "2020-02-00", "journal": {"title": "Nat Chem", "issn": "1755-4349", "volume": "12", "issue": "2", "pages": "145-158", "issn-l": null}, "abstract": "New drugs are desperately needed to combat methicillin-resistant Staphylococcus aureus (MRSA) infections. Here, we report screening commercial kinase inhibitors for antibacterial activity and found the anticancer drug sorafenib as major hit that effectively kills MRSA strains. Varying the key structural features led to the identification of a potent analogue, PK150, that showed antibacterial activity against several pathogenic strains at submicromolar concentrations. Furthermore, this antibiotic eliminated challenging persisters as well as established biofilms. PK150 holds promising therapeutic potential as it did not induce in vitro resistance, and shows oral bioavailability and in vivo efficacy. Analysis of the mode of action using chemical proteomics revealed several targets, which included interference with menaquinone biosynthesis by inhibiting demethylmenaquinone methyltransferase and the stimulation of protein secretion by altering the activity of signal peptidase IB. Reduced endogenous menaquinone levels along with enhanced levels of extracellular proteins of PK150-treated bacteria support this target hypothesis. The associated antibiotic effects, especially the lack of resistance development, probably stem from the compound's polypharmacology.", "doi": "10.1038/s41557-019-0378-7", "pmid": "31844194", "labels": [], "xrefs": [{"db": "mid", "key": "EMS84651"}, {"db": "pmc", "key": "PMC6994260"}, {"db": "pii", "key": "10.1038/s41557-019-0378-7"}], "notes": [], "created": "2026-08-21T11:50:26.696Z", "modified": "2026-08-21T11:50:26.935Z"}]}