{"entity": "researcher", "timestamp": "2026-08-23T13:31:40.357Z", "family": "Korotkov", "given": "Vadim S", "initials": "VS", "orcid": "0000-0003-3970-2483", "affiliations": ["Department of Chemistry, Center for Integrated Protein Science Munich (CIPSM), Technische Universit\u00e4t M\u00fcnchen, Lichtenbergstra\u00dfe 4, 85747, Garching, Germany."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/99f1fc62226b478a86ac5da5be09e39e.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/99f1fc62226b478a86ac5da5be09e39e"}}, "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"}, {"entity": "publication", "iuid": "90415ee5aa1349ef8a6ec14d830ace32", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/90415ee5aa1349ef8a6ec14d830ace32.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/90415ee5aa1349ef8a6ec14d830ace32"}}, "title": "Selective Activation of Human Caseinolytic Protease P (ClpP).", "authors": [{"family": "Stahl", "given": "Matthias", "initials": "M", "orcid": "0000-0002-0176-9386", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e51ba23ba70a47bba2d5fa5de3610b2e.json"}}, {"family": "Korotkov", "given": "Vadim S", "initials": "VS", "orcid": "0000-0003-3970-2483", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/99f1fc62226b478a86ac5da5be09e39e.json"}}, {"family": "Balogh", "given": "D\u00f3ra", "initials": "D"}, {"family": "Kick", "given": "Leonhard M", "initials": "LM", "orcid": "0000-0001-5231-208X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ef2d0aaeaa3843088eee6d460854491a.json"}}, {"family": "Gersch", "given": "Malte", "initials": "M"}, {"family": "Pahl", "given": "Axel", "initials": "A"}, {"family": "Kielkowski", "given": "Pavel", "initials": "P"}, {"family": "Richter", "given": "Klaus", "initials": "K"}, {"family": "Schneider", "given": "Sabine", "initials": "S", "orcid": "0000-0003-1054-8689", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6a735346a5ac4603b0f85f3b1112e996.json"}}, {"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": "2018-10-26", "journal": {"title": "Angew. Chem. Int. Ed. Engl.", "issn": "1521-3773", "volume": "57", "issue": "44", "pages": "14602-14607", "issn-l": "1433-7851"}, "abstract": "Caseinolytic protease P (ClpP) is the proteolytic component of the ClpXP protein degradation complex. Eukaryotic ClpP was recently found to act within the mitochondria-specific unfolded protein response (UPRmt ). However, its detailed function and dedicated regulation remain largely unexplored. A small molecule (D9) acts as a potent and species-selective activator of human ClpP (hClpP) by mimicking the natural chaperone ClpX. Structure-activity relationship studies highlight the importance of a halogenated benzyl motif within D9 that interacts with a unique aromatic amino acid network in hClpP. Mutational and structural studies suggest that this YYW motif tightly controls hClpP activity and regulates substrate turnover by interaction with cognate ligands. This signature motif is unique to ClpP from higher organisms and does not exist in tested bacterial homologues, allowing a species-selective analysis. Thus, D9 is a versatile tool to analyze mechanistic features of hClpP.", "doi": "10.1002/anie.201808189", "pmid": "30129683", "labels": [], "xrefs": [], "notes": [], "created": "2026-08-21T11:00:09.220Z", "modified": "2026-08-21T11:00:09.425Z"}]}