{"entity": "journal", "iuid": "4311ca36290b436e917dffe617037acc", "timestamp": "2026-08-11T14:48:23.158Z", "links": {"self": {"href": "https://publications.scilifelab.se/journal/Bioorg.%20Med.%20Chem.%20Lett..json"}, "display": {"href": "https://publications.scilifelab.se/journal/Bioorg.%20Med.%20Chem.%20Lett."}}, "title": "Bioorg. Med. Chem. Lett.", "issn": "1464-3405", "issn-l": "0960-894X", "publications_count": 6, "publications": [{"entity": "publication", "iuid": "e202d7f45983406db8e9f04f3f572696", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e202d7f45983406db8e9f04f3f572696.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e202d7f45983406db8e9f04f3f572696"}}, "title": "Discovery of USP7 small-molecule allosteric inhibitors.", "authors": [{"family": "Engstr\u00f6m", "given": "Olof", "initials": "O"}, {"family": "Belda", "given": "Oscar", "initials": "O"}, {"family": "Kullman-Magnusson", "given": "Mari", "initials": "M"}, {"family": "Rapp", "given": "Mikaela", "initials": "M"}, {"family": "B\u00f6hm", "given": "Kerstin", "initials": "K"}, {"family": "Paul", "given": "Ralf", "initials": "R"}, {"family": "Henderson", "given": "Ian", "initials": "I"}, {"family": "Derbyshire", "given": "Dean", "initials": "D"}, {"family": "Karlstr\u00f6m", "given": "Sofia", "initials": "S"}, {"family": "Parkes", "given": "Kevin E B", "initials": "KEB"}, {"family": "Zhao", "given": "Hongtao", "initials": "H", "orcid": "0000-0002-9318-1052", "researcher": {"href": "https://publications.scilifelab.se/researcher/84eabf78ece645598d2317049bfa38a4.json"}}], "type": "journal article", "published": "2020-10-15", "journal": {"title": "Bioorg. Med. Chem. Lett.", "issn": "1464-3405", "volume": "30", "issue": "20", "pages": "127471", "issn-l": "0960-894X"}, "abstract": "Ubiquitin specific protease-7 (USP7) is considered an attractive target for cancer therapy by promoting degradation of the tumor suppressor p53 and negatively affecting the immune response to tumors. However, the development of selective non-covalent USP7 inhibitors has proven challenging. In this work we report the NMR characterization of a weak binder from SPR screening of an in-house fragment library which reveals that it binds to the allosteric palm site of the catalytic domain. Molecular modeling combined with 1HNMR saturation transfer difference and NOESY experiments enabled structure-based design of additional compounds showing IC50 values in the low-micromolar range with good selectivity over the closest homolog USP47. The most potent analogue represents a promising starting point for the development of novel, selective USP7 inhibitors.", "doi": "10.1016/j.bmcl.2020.127471", "pmid": "32781219", "labels": {"Swedish NMR Centre": "Service"}, "xrefs": [{"db": "pii", "key": "S0960-894X(20)30582-5"}], "notes": [], "created": "2020-12-11T09:13:08.944Z", "modified": "2025-10-17T13:03:56.617Z"}, {"entity": "publication", "iuid": "f9b3f267ecd5422f97763146bba29f73", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f9b3f267ecd5422f97763146bba29f73.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f9b3f267ecd5422f97763146bba29f73"}}, "title": "Profiling of in vitro activities of urea-based inhibitors against cysteine synthases from Mycobacterium tuberculosis.", "authors": [{"family": "Brunner", "given": "Katharina", "initials": "K"}, {"family": "Steiner", "given": "Eva Maria", "initials": "EM"}, {"family": "Reshma", "given": "Rudraraju Srilakshmi", "initials": "RS"}, {"family": "Sriram", "given": "Dharmarajan", "initials": "D"}, {"family": "Schnell", "given": "Robert", "initials": "R"}, {"family": "Schneider", "given": "Gunter", "initials": "G"}], "type": "journal article", "published": "2017-10-01", "journal": {"title": "Bioorg. Med. Chem. Lett.", "issn": "1464-3405", "issn-l": "0960-894X", "volume": "27", "issue": "19", "pages": "4582-4587"}, "abstract": "CysK1 and CysK2 are two members of the cysteine/S-sulfocysteine synthase family in Mycobacterium tuberculosis, responsible for the de novo biosynthesis of l-cysteine, which is subsequently used as a building block for mycothiol. This metabolite is the first line defense of this pathogen against reactive oxygen and nitrogen species released by host macrophages after phagocytosis. In a previous medicinal chemistry campaign we had developed urea-based inhibitors of the cysteine synthase CysM with bactericidal activity against dormant M. tuberculosis. In this study we extended these efforts by examination of the in vitro activities of a library consisting of 71 urea compounds against CysK1 and CysK2. Binding was established by fluorescence spectroscopy and inhibition by enzyme assays. Several of the compounds inhibited these two cysteine synthases, with the most potent inhibitor displaying an IC50 value of 2.5\u00b5M for CysK1 and 6.6\u00b5M for CysK2, respectively. Four of the identified molecules targeting CysK1 and CysK2 were also among the top ten inhibitors of CysM, suggesting that potent compounds could be developed with activity against all three enzymes.", "doi": "10.1016/j.bmcl.2017.08.039", "pmid": "28882483", "labels": {"Protein Science Facility (PSF)": "Service", "Chemical Biology Consortium Sweden": "Service"}, "xrefs": [{"db": "pii", "key": "S0960-894X(17)30840-5"}], "notes": [], "created": "2017-10-24T06:16:47.963Z", "modified": "2025-10-17T13:04:29.106Z"}, {"entity": "publication", "iuid": "67cef94833744aff8d5931288cde32a1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/67cef94833744aff8d5931288cde32a1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/67cef94833744aff8d5931288cde32a1"}}, "title": "Diverse heterocyclic scaffolds as dCTP pyrophosphatase 1 inhibitors. Part 1: Triazoles, triazolopyrimidines, triazinoindoles, quinoline hydrazones and arylpiperazines.", "authors": [{"family": "Llona-Minguez", "given": "Sabin", "initials": "S"}, {"family": "H\u00e4ggblad", "given": "Maria", "initials": "M"}, {"family": "Martens", "given": "Ulf", "initials": "U"}, {"family": "Throup", "given": "Adam", "initials": "A"}, {"family": "Loseva", "given": "Olga", "initials": "O"}, {"family": "Jemth", "given": "Ann-Sofie", "initials": "AS"}, {"family": "Lundgren", "given": "Bo", "initials": "B"}, {"family": "Scobie", "given": "Martin", "initials": "M"}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d7256c271ea4adea404d4ff355f804e.json"}}], "type": "journal article", "published": "2017-08-15", "journal": {"volume": "27", "issn": "1464-3405", "issue": "16", "pages": "3897-3904", "title": "Bioorg. Med. Chem. Lett.", "issn-l": "0960-894X"}, "abstract": "A high-throughput screening campaign using a commercial compound library (ChemBridge DiverSET) revealed diverse chemotypes as inhibitors of the human dCTP pyrophosphatase 1 (dCTPase). Triazole, triazolopyrimidine, triazinoindole, quinoline hydrazone and arylpiperazine hits were clustered, confirmed by IC50 determinations, and their preliminary structure-activity-relationships (SAR) and ligand efficiency scores are discussed in this letter.", "doi": "10.1016/j.bmcl.2017.06.038", "pmid": "28687206", "labels": {"Drug Discovery and Development": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S0960-894X(17)30640-6"}], "notes": "Biochemical and Cellular Screening", "created": "2017-11-01T09:58:40.357Z", "modified": "2025-10-17T13:05:08.785Z"}, {"entity": "publication", "iuid": "8b7c4d6802d344fb9c124aae688ece80", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8b7c4d6802d344fb9c124aae688ece80.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8b7c4d6802d344fb9c124aae688ece80"}}, "title": "Diverse heterocyclic scaffolds as dCTP pyrophosphatase 1 inhibitors. Part 2: Pyridone- and pyrimidinone-derived systems.", "authors": [{"family": "Llona-Minguez", "given": "Sabin", "initials": "S"}, {"family": "H\u00e4ggblad", "given": "Maria", "initials": "M"}, {"family": "Martens", "given": "Ulf", "initials": "U"}, {"family": "Johansson", "given": "Lars", "initials": "L"}, {"family": "Sigmundsson", "given": "Kristmundur", "initials": "K"}, {"family": "Lundb\u00e4ck", "given": "Thomas", "initials": "T"}, {"family": "Loseva", "given": "Olga", "initials": "O"}, {"family": "Jemth", "given": "Ann-Sofie", "initials": "AS"}, {"family": "Lundgren", "given": "Bo", "initials": "B"}, {"family": "Jensen", "given": "Annika Jenmalm", "initials": "AJ"}, {"family": "Scobie", "given": "Martin", "initials": "M"}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d7256c271ea4adea404d4ff355f804e.json"}}], "type": "journal article", "published": "2017-08-01", "journal": {"volume": "27", "issn": "1464-3405", "issue": "15", "pages": "3219-3225", "title": "Bioorg. Med. Chem. Lett.", "issn-l": "0960-894X"}, "abstract": "Two screening campaigns using commercial (Chembridge DiverSET) and proprietary (Chemical Biology Consortium Sweden, CBCS) compound libraries, revealed a number of pyridone- and pyrimidinone-derived systems as inhibitors of the human dCTP pyrophosphatase 1 (dCTPase). In this letter, we present their preliminary structure-activity-relationships (SAR) and ligand efficiency scores (LE and LLE).", "doi": "10.1016/j.bmcl.2017.06.039", "pmid": "28655422", "labels": {"Chemical Biology Consortium Sweden": "Collaborative", "Drug Discovery and Development": "Service"}, "xrefs": [{"db": "pii", "key": "S0960-894X(17)30641-8"}], "notes": "Biochemical and Cellular Screening", "created": "2017-10-31T13:29:22.883Z", "modified": "2025-10-17T13:05:08.796Z"}, {"entity": "publication", "iuid": "d8d46dfc517c4e59bc0d65cc9ef7bab9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d8d46dfc517c4e59bc0d65cc9ef7bab9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d8d46dfc517c4e59bc0d65cc9ef7bab9"}}, "title": "Kinetic investigation of human 5-lipoxygenase with arachidonic acid.", "authors": [{"family": "Mittal", "given": "Monica", "initials": "M"}, {"family": "Kumar", "given": "Ramakrishnan B", "initials": "RB"}, {"family": "Balagunaseelan", "given": "Navisraj", "initials": "N"}, {"family": "Hamberg", "given": "Mats", "initials": "M"}, {"family": "Jegersch\u00f6ld", "given": "Caroline", "initials": "C"}, {"family": "R\u00e5dmark", "given": "Olof", "initials": "O"}, {"family": "Haeggstr\u00f6m", "given": "Jesper Z", "initials": "JZ"}, {"family": "Rinaldo-Matthis", "given": "Agnes", "initials": "A"}], "type": "journal article", "published": "2016-08-01", "journal": {"volume": "26", "issn": "1464-3405", "issue": "15", "pages": "3547-3551", "title": "Bioorg. Med. Chem. Lett.", "issn-l": "0960-894X"}, "abstract": "Human 5-lipoxygenase (5-LOX) is responsible for the formation of leukotriene (LT)A4, a pivotal intermediate in the biosynthesis of the leukotrienes, a family of proinflammatory lipid mediators. 5-LOX has thus gained attention as a potential drug target. However, details of the kinetic mechanism of 5-LOX are still obscure. In this Letter, we investigated the kinetic isotope effect (KIE) of 5-LOX with its physiological substrate, arachidonic acid (AA). The observed KIE is 20\u00b14 on kcat and 17\u00b12 on kcat/KM at 25\u00b0C indicating a non-classical reaction mechanism. The observed rates show slight temperature dependence at ambient temperatures ranging from 4 to 35\u00b0C. Also, we observed low Arrhenius prefactor ratio (AH/AD=0.21) and a small change in activation energy (Ea(D)-Ea(H)=3.6J/mol) which suggests that 5-LOX catalysis involves tunneling as a mechanism of H-transfer. The measured KIE for 5-LOX involves a change in regioselectivity in response to deuteration at position C7, resulting in H-abstraction form C10 and formation of 8-HETE. The viscosity experiments influence the (H)kcat, but not (D)kcat. However the overall kcat/KM is not affected for labeled or unlabeled AA, suggesting that either the product release or conformational rearrangement might be involved in dictating kinetics of 5-LOX at saturating conditions. Investigation of available crystal structures suggests the role of active site residues (F421, Q363 and L368) in regulating the donor-acceptor distances, thus affecting H-transfer as well as regiospecificity. In summary, our study shows that that the H-abstraction is the rate limiting step for 5-LOX and that the observed KIE of 5-LOX is masked by a change in regioselectivity.", "doi": "10.1016/j.bmcl.2016.06.025", "pmid": "27363940", "labels": {"Protein Science Facility (PSF)": "Service"}, "xrefs": [{"db": "pii", "key": "S0960-894X(16)30636-9"}], "notes": [], "created": "2017-05-03T13:02:39.816Z", "modified": "2017-09-06T11:42:09.414Z"}, {"entity": "publication", "iuid": "39ea1e478b8241e280e93e84e39c1fc8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/39ea1e478b8241e280e93e84e39c1fc8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/39ea1e478b8241e280e93e84e39c1fc8"}}, "title": "Derivatives of 8-hydroxyquinoline--antibacterial agents that target intra- and extracellular Gram-negative pathogens.", "authors": [{"family": "Enquist", "given": "Per-Anders", "initials": "P"}, {"family": "Gylfe", "given": "Asa", "initials": "A"}, {"family": "H\u00e4gglund", "given": "Ulrik", "initials": "U"}, {"family": "Lindstr\u00f6m", "given": "Pia", "initials": "P"}, {"family": "Norberg-Scherman", "given": "Henrik", "initials": "H"}, {"family": "Sundin", "given": "Charlotta", "initials": "C"}, {"family": "Elofsson", "given": "Mikael", "initials": "M"}], "type": "journal article", "published": "2012-05-15", "journal": {"volume": "22", "issn": "1464-3405", "issue": "10", "pages": "3550-3553", "title": "Bioorg. Med. Chem. Lett.", "issn-l": "0960-894X"}, "abstract": "Small molecule screening identified 5-nitro-7-((4-phenylpiperazine-1-yl-)methyl)quinolin-8-ol INP1750 as a putative inhibitor of type III secretion (T3S) in the Gram-negative pathogen Yersinia pseudotuberculosis. In this study we report structure-activity relationships for inhibition of T3S and show that the most potent compounds target both the extracellular bacterium Y. pseudotuberculosis and the intracellular pathogen Chlamydia trachomatis in cell-based infection models.", "doi": "10.1016/j.bmcl.2012.03.096", "pmid": "22525317", "labels": {"Chemical Biology Consortium Sweden": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S0960-894X(12)00426-X"}], "notes": "Laboratories for Chemical Biology Ume\u00e5 (LCBU)", "created": "2017-05-04T14:56:38.521Z", "modified": "2025-10-17T13:04:30.666Z"}], "created": "2017-05-09T09:12:05.933Z", "modified": "2020-11-27T13:14:03.074Z"}