{"entity": "researcher", "timestamp": "2026-08-20T20:45:55.033Z", "family": "Barlow", "given": "Nicholas", "initials": "N", "orcid": "0000-0002-5749-3542", "affiliations": ["Department of Medicinal Chemistry , BMC , Uppsala University , P.O. Box 574 , SE-751 23 Uppsala , Sweden.", "Medicinal Chemistry , Monash Institute of Pharmaceutical Sciences , Parkville , Victoria 3052 , Australia . Email: philip.thompson@monash.edu."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/a67b60d6fd4048d6b34766c0dfc82547.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/a67b60d6fd4048d6b34766c0dfc82547"}}, "publications": [{"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": "347e12b5e010425cae36b0a03d10b72e", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/347e12b5e010425cae36b0a03d10b72e.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/347e12b5e010425cae36b0a03d10b72e"}}, "title": "Macrocyclic peptidomimetics as inhibitors of insulin-regulated aminopeptidase (IRAP).", "authors": [{"family": "Barlow", "given": "Nicholas", "initials": "N", "orcid": "0000-0002-5749-3542", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a67b60d6fd4048d6b34766c0dfc82547.json"}}, {"family": "Vanga", "given": "Sudarsana Reddy", "initials": "SR"}, {"family": "S\u00e4vmarker", "given": "Jonas", "initials": "J"}, {"family": "Sandstr\u00f6m", "given": "Anja", "initials": "A"}, {"family": "Burns", "given": "Peta", "initials": "P"}, {"family": "Hallberg", "given": "Anders", "initials": "A"}, {"family": "\u00c5qvist", "given": "Johan", "initials": "J"}, {"family": "Guti\u00e9rrez-de-Ter\u00e1n", "given": "Hugo", "initials": "H"}, {"family": "Hallberg", "given": "Mathias", "initials": "M", "orcid": "0000-0002-9835-870X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/76184702a3c14996a2ab9db8ffdbe19f.json"}}, {"family": "Larhed", "given": "Mats", "initials": "M", "orcid": "0000-0001-6258-0635", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/225695195abc4233bd141e6858e72e7f.json"}}, {"family": "Chai", "given": "Siew Yeen", "initials": "SY", "orcid": "0000-0001-7209-4112", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1ed844df0afe48c3928a8707886ec681.json"}}, {"family": "Thompson", "given": "Philip E", "initials": "PE", "orcid": "0000-0002-5910-7625", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8d855f9d000e43b1afa8f07d062c8c8a.json"}}], "type": "journal article", "published": "2020-02-01", "journal": {"title": "RSC Med Chem", "issn": "2632-8682", "volume": "11", "issue": "2", "pages": "234-244", "issn-l": null}, "abstract": "Macrocyclic analogues of the linear hexapeptide, angiotensin IV (AngIV) have proved to be potent inhibitors of insulin-regulated aminopeptidase (IRAP, oxytocinase, EC 3.4.11.3). Along with higher affinity, macrocycles may also offer better metabolic stability, membrane permeability and selectivity, however predicting the outcome of particular cycle modifications is challenging. Here we describe the development of a series of macrocyclic IRAP inhibitors with either disulphide, olefin metathesis or lactam bridges and variations of ring size and other functionality. The binding mode of these compounds is proposed based on molecular dynamics analysis. Estimation of binding affinities (\u0394G) and relative binding free energies (\u0394\u0394G) with the linear interaction energy (LIE) method and free energy perturbation (FEP) method showed good general agreement with the observed inhibitory potency. Experimental and calculated data highlight the cumulative importance of an intact N-terminal peptide, the specific nature of the macrocycle, the phenolic oxygen and the C-terminal functionality.", "doi": "10.1039/c9md00485h", "pmid": "33479630", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC7412577"}, {"db": "pii", "key": "c9md00485h"}], "notes": [], "created": "2026-08-20T09:27:13.786Z", "modified": "2026-08-20T09:27:13.994Z"}]}