{"entity": "researcher", "timestamp": "2026-08-20T20:42:28.903Z", "family": "Gising", "given": "Johan", "initials": "J", "orcid": "0000-0001-8852-6071", "affiliations": [], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/35360120fcd544faba8998acdcc6d5bc.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/35360120fcd544faba8998acdcc6d5bc"}}, "publications": [{"entity": "publication", "iuid": "5a1cabc3966c4bfc9331c7a709676084", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/5a1cabc3966c4bfc9331c7a709676084.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/5a1cabc3966c4bfc9331c7a709676084"}}, "title": "Benzylhydroxamic Acids as IRAP Inhibitors: Sulfonamide Variations", "authors": [{"family": "Larhed", "given": "Mats", "initials": "M", "orcid": "0000-0001-6258-0635", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/225695195abc4233bd141e6858e72e7f.json"}}, {"family": "Gising", "given": "Johan", "initials": "J", "orcid": "0000-0001-8852-6071", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/35360120fcd544faba8998acdcc6d5bc.json"}}, {"family": "Beveridge", "given": "Julia", "initials": "J", "orcid": "0000-0002-9425-8832", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f24567000ef3421286eb1f019071cac3.json"}}, {"family": "S\u00f6derstr\u00f6m", "given": "Marcus", "initials": "M"}, {"family": "Balestri", "given": "Lorenzo Jacopo Ilic", "initials": "LJI"}, {"family": "Prieto-D\u00edaz", "given": "Rub\u00e9n", "initials": "R"}, {"family": "Gutierrez-de-Teran", "given": "Hugo", "initials": "H"}, {"family": "Odell", "given": "Luke R", "initials": "LR", "orcid": "0000-0001-7658-5103", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/49395660c6af4fce9ad0f7f8fc793744.json"}}, {"family": "Hallberg", "given": "Mathias", "initials": "M"}], "type": "journal-article", "published": "2025-10-00", "journal": {"title": "Synlett", "issn": "0936-5214", "volume": "36", "issue": "16", "pages": "2666-2670", "issn-l": null}, "abstract": null, "doi": "10.1055/a-2562-7204", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T09:28:35.950Z", "modified": "2026-08-20T09:28:36.052Z"}, {"entity": "publication", "iuid": "e28e0ff6eea04d33b55d4d01075bcfac", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/e28e0ff6eea04d33b55d4d01075bcfac.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/e28e0ff6eea04d33b55d4d01075bcfac"}}, "title": "A Diastereoselective Mizoroki\u2013Heck Reaction for Synthesis of Spirooxindole-Based Nonnatural Amino Acids Using a Boc-Protected Amine Chiral Auxiliary", "authors": [{"family": "Larhed", "given": "Mats", "initials": "M", "orcid": "0000-0001-6258-0635", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/225695195abc4233bd141e6858e72e7f.json"}}, {"family": "Lindman", "given": "Jens", "initials": "J"}, {"family": "Puthiyaparambath", "given": "Sharathna", "initials": "S"}, {"family": "Gising", "given": "Johan", "initials": "J", "orcid": "0000-0001-8852-6071", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/35360120fcd544faba8998acdcc6d5bc.json"}}, {"family": "Odell", "given": "Luke R", "initials": "LR", "orcid": "0000-0001-7658-5103", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/49395660c6af4fce9ad0f7f8fc793744.json"}}], "type": "journal-article", "published": "2025-09-00", "journal": {"title": "Synlett", "issn": "0936-5214", "volume": "36", "issue": "14", "pages": "2009-2013", "issn-l": null}, "abstract": null, "doi": "10.1055/a-2564-4920", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T09:28:37.751Z", "modified": "2026-08-20T09:28:37.840Z"}, {"entity": "publication", "iuid": "922c362323994d3ebed2a330945edbf1", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/922c362323994d3ebed2a330945edbf1.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/922c362323994d3ebed2a330945edbf1"}}, "title": "Benzylhydroxamic acids as inhibitors of insulin regulated aminopeptidase (IRAP)", "authors": [{"family": "Beveridge", "given": "Julia", "initials": "J", "orcid": "0000-0002-9425-8832", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f24567000ef3421286eb1f019071cac3.json"}}, {"family": "S\u00f6derstr\u00f6m", "given": "Marcus", "initials": "M", "orcid": "0000-0002-5611-1733", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b68f9a3dadf74fcda147dd097c701dae.json"}}, {"family": "Prieto-D\u00edaz", "given": "Rub\u00e9n", "initials": "R", "orcid": "0000-0003-2539-3106", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5554a64a2dd64a8ca1ac3b7b1ddcf98d.json"}}, {"family": "Gutierrez-de-Teran", "given": "Hugo", "initials": "H"}, {"family": "Odell", "given": "Luke R", "initials": "LR"}, {"family": "Hallberg", "given": "Mathias", "initials": "M"}, {"family": "Larhed", "given": "Mats", "initials": "M"}, {"family": "Gising", "given": "Johan", "initials": "J", "orcid": "0000-0001-8852-6071", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/35360120fcd544faba8998acdcc6d5bc.json"}}], "type": "journal-article", "published": "2024-12-00", "journal": {"title": "European Journal of Medicinal Chemistry Reports", "issn": "2772-4174", "volume": "12", "pages": "100215", "issn-l": null}, "abstract": null, "doi": "10.1016/j.ejmcr.2024.100215", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T07:54:33.094Z", "modified": "2026-08-20T07:54:33.285Z"}, {"entity": "publication", "iuid": "c54b915ee83742c09ee7121dc8dec5a5", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/c54b915ee83742c09ee7121dc8dec5a5.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/c54b915ee83742c09ee7121dc8dec5a5"}}, "title": "Inhibition of IRAP Enhances the Expression of Pro-Cognitive Markers Drebrin and MAP2 in Rat Primary Neuronal Cells.", "authors": [{"family": "Stam", "given": "Frida", "initials": "F"}, {"family": "Bjurling", "given": "Sara", "initials": "S"}, {"family": "Nylander", "given": "Erik", "initials": "E", "orcid": "0000-0002-9683-6034", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6c44bdb91fce4b53ac2eff374bbf9c00.json"}}, {"family": "H\u00e5kansson", "given": "Esther Olaniran", "initials": "EO"}, {"family": "Barlow", "given": "Nicholas", "initials": "N", "orcid": "0000-0002-5749-3542", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a67b60d6fd4048d6b34766c0dfc82547.json"}}, {"family": "Gising", "given": "Johan", "initials": "J", "orcid": "0000-0001-8852-6071", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/35360120fcd544faba8998acdcc6d5bc.json"}}, {"family": "Larhed", "given": "Mats", "initials": "M", "orcid": "0000-0001-6258-0635", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/225695195abc4233bd141e6858e72e7f.json"}}, {"family": "Odell", "given": "Luke R", "initials": "LR"}, {"family": "Gr\u00f6nbladh", "given": "Alfhild", "initials": "A", "orcid": "0000-0001-9780-4168", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/43805f4c399d4ba9b6a3e62a5081cef2.json"}}, {"family": "Hallberg", "given": "Mathias", "initials": "M", "orcid": "0000-0002-9835-870X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/76184702a3c14996a2ab9db8ffdbe19f.json"}}], "type": "journal article", "published": "2024-11-08", "journal": {"title": "Int J Mol Sci", "issn": "1422-0067", "volume": "25", "issue": "22", "issn-l": null}, "abstract": "The insulin-regulated aminopeptidase (IRAP; oxytocinase) is part of the M1 aminopeptidase family and is highly expressed in many tissues, including the neocortex and hippocampus of the brain. IRAP is involved in various physiological functions and has been identified as a receptor for the endogenous hexapeptide Angiotensin IV (Ang IV). The binding of Ang IV inhibits the enzymatic activity of IRAP and has been proven to enhance learning and memory in animal models. The macrocyclic compound 9 (C9) is a potent synthetic IRAP inhibitor developed from the previously reported inhibitor HA08. In this study, we have examined compound C9 and its effects on cognitive markers drebrin, microtubule-associated protein 2 (MAP2), and glial fibrillary acidic protein (GFAP) in primary hippocampal and cortical cultures. Cells from Sprague Dawley rats were cultured for 14 days before treatment with C9 for 4 consecutive days. The cells were analysed for protein expression of drebrin, MAP2, GFAP, glucose transporter type 4 (GLUT4), vesicular glutamate transporter 1 (vGluT1), and synapsin I using immunocytochemistry. The gene expression of related proteins was determined using qPCR, and viability assays were performed to evaluate toxicity. The results showed that protein expression of drebrin and MAP2 was increased, and the corresponding mRNA levels were decreased after treatment with C9 in the hippocampal cultures. The ratio of MAP2-positive neurons and GFAP-positive astrocytes was altered and there were no toxic effects observed. In conclusion, the IRAP inhibitor compound C9 enhances the expression of the pro-cognitive markers drebrin and MAP2, which further confirms IRAP as a relevant pharmaceutical target and C9 as a promising candidate for further investigation.", "doi": "10.3390/ijms252212016", "pmid": "39596085", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11594062"}, {"db": "pii", "key": "ijms252212016"}], "notes": [], "created": "2026-08-20T13:41:58.326Z", "modified": "2026-08-20T13:41:58.446Z"}, {"entity": "publication", "iuid": "1888a6a69811421c88b2f0f897864384", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/1888a6a69811421c88b2f0f897864384.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/1888a6a69811421c88b2f0f897864384"}}, "title": "Inhibition of IRAP Enhance the Expression of Pro-cognitive Markers Drebrin and MAP2 in Rat Primary Neuronal Cells", "authors": [{"family": "Stam", "given": "Frida", "initials": "F"}, {"family": "Bjurling", "given": "Sara", "initials": "S"}, {"family": "Nylander", "given": "Erik", "initials": "E"}, {"family": "Olaniran H\u00e5kansson", "given": "Esther", "initials": "E"}, {"family": "Barlow", "given": "Nicholas", "initials": "N", "orcid": "0000-0002-5749-3542", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a67b60d6fd4048d6b34766c0dfc82547.json"}}, {"family": "Gising", "given": "Johan", "initials": "J", "orcid": "0000-0001-8852-6071", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/35360120fcd544faba8998acdcc6d5bc.json"}}, {"family": "Larhed", "given": "Mats", "initials": "M", "orcid": "0000-0001-6258-0635", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/225695195abc4233bd141e6858e72e7f.json"}}, {"family": "Odell", "given": "Luke R", "initials": "LR"}, {"family": "Gr\u00f6nbladh", "given": "Alfhild", "initials": "A"}, {"family": "Hallberg", "given": "Mathias", "initials": "M"}], "type": "posted-content", "published": "2024-07-31", "journal": {"issn-l": null}, "abstract": null, "doi": "10.20944/preprints202407.2523.v1", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T12:56:40.055Z", "modified": "2026-08-20T12:56:40.138Z"}, {"entity": "publication", "iuid": "3c64f59b59394580bc404609d7606bed", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/3c64f59b59394580bc404609d7606bed.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/3c64f59b59394580bc404609d7606bed"}}, "title": "The Discovery of New Inhibitors of Insulin-Regulated Aminopeptidase by a High-Throughput Screening of 400,000 Drug-like Compounds.", "authors": [{"family": "Gising", "given": "Johan", "initials": "J", "orcid": "0000-0001-8852-6071", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/35360120fcd544faba8998acdcc6d5bc.json"}}, {"family": "Honarnejad", "given": "Saman", "initials": "S", "orcid": "0000-0002-4558-501X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/138a2199f9504b9fa96c3c963e820b21.json"}}, {"family": "Bras", "given": "Maaike", "initials": "M"}, {"family": "Baillie", "given": "Gemma L", "initials": "GL"}, {"family": "McElroy", "given": "Stuart P", "initials": "SP", "orcid": "0000-0002-5182-2616", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6c4e720e5e2946ecb4d2d32ea12818a6.json"}}, {"family": "Jones", "given": "Philip S", "initials": "PS"}, {"family": "Morrison", "given": "Angus", "initials": "A"}, {"family": "Beveridge", "given": "Julia", "initials": "J", "orcid": "0000-0002-9425-8832", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f24567000ef3421286eb1f019071cac3.json"}}, {"family": "Hallberg", "given": "Mathias", "initials": "M"}, {"family": "Larhed", "given": "Mats", "initials": "M", "orcid": "0000-0001-6258-0635", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/225695195abc4233bd141e6858e72e7f.json"}}], "type": "journal article", "published": "2024-04-06", "journal": {"title": "Int J Mol Sci", "issn": "1422-0067", "volume": "25", "issue": "7", "issn-l": null}, "abstract": "With the ambition to identify novel chemical starting points that can be further optimized into small drug-like inhibitors of insulin-regulated aminopeptidase (IRAP) and serve as potential future cognitive enhancers in the clinic, we conducted an ultra-high-throughput screening campaign of a chemically diverse compound library of approximately 400,000 drug-like small molecules. Three biochemical and one biophysical assays were developed to enable large-scale screening and hit triaging. The screening funnel, designed to be compatible with high-density microplates, was established with two enzyme inhibition assays employing either fluorescent or absorbance readouts. As IRAP is a zinc-dependent enzyme, the remaining active compounds were further evaluated in the primary assay, albeit with the addition of zinc ions. Rescreening with zinc confirmed the inhibitory activity for most compounds, emphasizing a zinc-independent mechanism of action. Additionally, target engagement was confirmed using a complementary biophysical thermal shift assay where compounds causing positive/negative thermal shifts were considered genuine binders. Triaging based on biochemical activity, target engagement, and drug-likeness resulted in the selection of 50 qualified hits, of which the IC50 of 32 compounds was below 3.5 \u00b5M. Despite hydroxamic acid dominance, diverse chemotypes with biochemical activity and target engagement were discovered, including non-hydroxamic acid compounds. The most potent compound (QHL1) was resynthesized with a confirmed inhibitory IC50 of 320 nM. Amongst these compounds, 20 new compound structure classes were identified, providing many new starting points for the development of unique IRAP inhibitors. Detailed characterization and optimization of lead compounds, considering both hydroxamic acids and other diverse structures, are in progress for further exploration.", "doi": "10.3390/ijms25074084", "pmid": "38612894", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11012289"}, {"db": "pii", "key": "ijms25074084"}], "notes": [], "created": "2026-08-20T13:41:47.032Z", "modified": "2026-08-20T13:41:47.226Z"}, {"entity": "publication", "iuid": "346c4ade3b754191842578052e228656", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/346c4ade3b754191842578052e228656.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/346c4ade3b754191842578052e228656"}}, "title": "Hydrogen Peroxide Induced Toxicity Is Reversed by the Macrocyclic IRAP-Inhibitor HA08 in Primary Hippocampal Cell Cultures.", "authors": [{"family": "Stam", "given": "Frida", "initials": "F"}, {"family": "Flor\u00e9n Lind", "given": "Sara", "initials": "S"}, {"family": "Schroff", "given": "Anja", "initials": "A"}, {"family": "Zelleroth", "given": "Sofia", "initials": "S"}, {"family": "Nylander", "given": "Erik", "initials": "E", "orcid": "0000-0002-9683-6034", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6c44bdb91fce4b53ac2eff374bbf9c00.json"}}, {"family": "Gising", "given": "Johan", "initials": "J", "orcid": "0000-0001-8852-6071", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/35360120fcd544faba8998acdcc6d5bc.json"}}, {"family": "Gr\u00f6nbladh", "given": "Alfhild", "initials": "A", "orcid": "0000-0001-9780-4168", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/43805f4c399d4ba9b6a3e62a5081cef2.json"}}, {"family": "Larhed", "given": "Mats", "initials": "M", "orcid": "0000-0001-6258-0635", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/225695195abc4233bd141e6858e72e7f.json"}}, {"family": "Hallberg", "given": "Mathias", "initials": "M", "orcid": "0000-0002-9835-870X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/76184702a3c14996a2ab9db8ffdbe19f.json"}}], "type": "journal article", "published": "2022-10-18", "journal": {"title": "Curr Issues Mol Biol", "issn": "1467-3045", "volume": "44", "issue": "10", "pages": "5000-5012", "issn-l": null}, "abstract": "Angiotensin IV (Ang IV), a metabolite of Angiotensin II, is a bioactive hexapeptide that inhibits the insulin-regulated aminopeptidase (IRAP). This transmembrane zinc metallopeptidase with many biological functions has in recent years emerged as a new pharmacological target. IRAP is expressed in a variety of tissues and can be found in high density in the hippocampus and neocortex, brain regions associated with cognition. Ang IV is known to improve memory tasks in experimental animals. One of the most potent IRAP inhibitors known today is the macrocyclic compound HA08 that is significantly more stable than the endogenous Ang IV. HA08 combines structural elements from Ang IV and the physiological substrates oxytocin and vasopressin, and binds to the catalytic site of IRAP. In the present study we evaluate whether HA08 can restore cell viability in rat primary cells submitted to hydrogen peroxide damage. After damaging the cells with hydrogen peroxide and subsequently treating them with HA08, the conceivable restoring effects of the IRAP inhibitor were assessed. The cellular viability was determined by measuring mitochondrial activity and lactate dehydrogenase (LDH) release. The mitochondrial activity was significantly higher in primary hippocampal cells, whereas the amount of LDH was unaffected. We conclude that the cell viability can be restored in this cell type by blocking IRAP with the potent macrocyclic inhibitor HA08, although the mechanism by which HA08 exerts its effects remains unclear.", "doi": "10.3390/cimb44100340", "pmid": "36286055", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC9601255"}, {"db": "pii", "key": "cimb44100340"}], "notes": [], "created": "2026-08-20T13:40:22.494Z", "modified": "2026-08-20T13:40:22.656Z"}]}