{"entity": "researcher", "timestamp": "2026-07-15T16:45:21.712Z", "family": "Wheelock", "given": "Craig E", "initials": "CE", "orcid": "0000-0002-8113-0653", "affiliations": ["Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden.", "Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/a3cd2b99e3e9486ba41030c809a48c51.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/a3cd2b99e3e9486ba41030c809a48c51"}}, "publications": [{"entity": "publication", "iuid": "e68983c84bbc41d8a88758e197b58a33", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e68983c84bbc41d8a88758e197b58a33.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e68983c84bbc41d8a88758e197b58a33"}}, "title": "Potent Neuronal Nicotinamide Adenine Dinucleotide-Boosting Tetrahydroquinoxalines: Structure-Activity Relationships and Early Drug Metabolism and Pharmacokinetics Evaluation.", "authors": [{"family": "Cu\u0159\u00ednov\u00e1", "given": "Petra", "initials": "P", "orcid": "0000-0001-8264-7032", "researcher": {"href": "https://publications.scilifelab.se/researcher/f196559d7e954e448879878768bc213e.json"}}, {"family": "J\u00f6e", "given": "Melissa", "initials": "M"}, {"family": "Cesar", "given": "Filip", "initials": "F"}, {"family": "Nicol", "given": "Alan", "initials": "A"}, {"family": "Schwan", "given": "Kristi\u00e1n", "initials": "K"}, {"family": "Kohout", "given": "Michal", "initials": "M", "orcid": "0000-0003-1447-4453", "researcher": {"href": "https://publications.scilifelab.se/researcher/a4f2547f153b43d79c0364607cd518c6.json"}}, {"family": "Varrichio", "given": "Carmine", "initials": "C"}, {"family": "Saleh", "given": "Aljona", "initials": "A"}, {"family": "Wheelock", "given": "Craig E", "initials": "CE", "orcid": "0000-0002-8113-0653", "researcher": {"href": "https://publications.scilifelab.se/researcher/a3cd2b99e3e9486ba41030c809a48c51.json"}}, {"family": "J\u00f3hannesson", "given": "Gauti", "initials": "G"}, {"family": "Eigner", "given": "V\u00e1clav", "initials": "V"}, {"family": "Tribble", "given": "James R", "initials": "JR"}, {"family": "Brancale", "given": "Andrea", "initials": "A", "orcid": "0000-0002-9728-3419", "researcher": {"href": "https://publications.scilifelab.se/researcher/7aa54df57e794ee3a2b98108bd694277.json"}}, {"family": "Williams", "given": "Pete A", "initials": "PA", "orcid": "0000-0001-6194-8397", "researcher": {"href": "https://publications.scilifelab.se/researcher/0b4d7eb42dcd4c489a97198a043b3806.json"}}], "type": "journal article", "published": "2026-04-09", "journal": {"title": "ACS Med Chem Lett", "issn": "1948-5875", "volume": "17", "issue": "4", "pages": "916-924", "issn-l": "1948-5875"}, "abstract": "We designed and synthesized a series of novel 1,2,3,4-tetrahydroquinoxaline derivatives and evaluated their ability to increase nicotinamide adenine dinucleotide (NAD) levels in primary cortical neurons. Several compounds demonstrated nanomolar potency and enabled the establishment of clear structure-activity relationships (SAR), highlighting key substituents required for activity. Qualitative 3DSAR analysis further identified favorable steric, electrostatic, and hydrophobic features associated with NAD enhancement. Selected lead compounds were assessed for in vitro drug metabolism and pharmacokinetics (DMPK) properties, showing good cell permeability and species-dependent metabolic stability in liver microsomes, with improved stability in human systems compared with rodent systems. 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"https://publications.scilifelab.se/researcher/5986cb3bab4b482c831862a85c85b238.json"}}, {"family": "Gaga", "given": "Mina", "initials": "M", "orcid": "0000-0002-9949-6012", "researcher": {"href": "https://publications.scilifelab.se/researcher/124934c35baf4fb89053532fcc354a96.json"}}, {"family": "Geiser", "given": "Thomas", "initials": "T"}, {"family": "Gjomarkaj", "given": "Mark", "initials": "M"}, {"family": "Horv\u00e1th", "given": "Ildik\u00f3", "initials": "I"}, {"family": "Howarth", "given": "Peter H", "initials": "PH", "orcid": "0000-0003-0619-7927", "researcher": {"href": "https://publications.scilifelab.se/researcher/ae17cd831edd48d7b851773eded77345.json"}}, {"family": "Johnston", "given": "Sebastian L", "initials": "SL"}, {"family": "Joos", "given": "Guy", "initials": "G", "orcid": "0000-0002-3149-9444", "researcher": {"href": "https://publications.scilifelab.se/researcher/f324289e94b844c980ff7be24032b9b3.json"}}, {"family": "Krug", "given": "Norbert", "initials": "N"}, {"family": "Montuschi", "given": "Paolo", "initials": "P"}, {"family": "Musial", "given": "Jacek", "initials": "J"}, {"family": "Ni\u017cankowska-Mogilnicka", "given": "Ewa", "initials": "E"}, {"family": "Olsson", "given": "Henric K", "initials": "HK"}, {"family": "Papi", "given": "Alberto", "initials": "A"}, {"family": "Rabe", "given": "Klaus F", "initials": "KF"}, {"family": "Sandstr\u00f6m", "given": "Thomas", "initials": "T"}, {"family": "Shaw", "given": "Dominick E", "initials": "DE", "orcid": "0000-0003-4106-8469", "researcher": {"href": "https://publications.scilifelab.se/researcher/56efd0f5f85a478493f8b25d23e371be.json"}}, {"family": "Siafakas", "given": "Nikolaos M", "initials": "NM"}, {"family": "Uhl\u00e9n", "given": "Mathias", "initials": "M"}, {"family": "Riley", "given": "John H", "initials": "JH"}, {"family": "Bates", "given": "Stewart", "initials": "S"}, {"family": "Middelveld", "given": "Roelinde J M", "initials": "RJM"}, {"family": "Wheelock", "given": "Craig E", "initials": "CE", "orcid": "0000-0002-8113-0653", "researcher": {"href": "https://publications.scilifelab.se/researcher/a3cd2b99e3e9486ba41030c809a48c51.json"}}, {"family": "Chung", "given": "Kian Fan", "initials": "KF"}, {"family": "Adcock", "given": "Ian M", "initials": "IM", "orcid": "0000-0003-2101-8843", "researcher": {"href": "https://publications.scilifelab.se/researcher/7ed3d714173144fabe2aa61165810992.json"}}, {"family": "Sterk", "given": "Peter J", "initials": "PJ"}, {"family": "Djukanovic", "given": "Ratko", "initials": "R"}, {"family": "Nilsson", "given": "Peter", "initials": "P", "orcid": "0000-0002-4657-8532", "researcher": {"href": "https://publications.scilifelab.se/researcher/799bcf1cf8cf451296f4535dd4ca9dc0.json"}}, {"family": "Dahl\u00e9n", "given": "Sven Erik", "initials": "SE"}, {"family": "James", "given": "Anna", "initials": "A"}], "type": "journal-article", "published": "2022-02-00", "journal": {"title": "Eur Respir J", "issn": "0903-1936", "issn-l": "0903-1936", "volume": "59", "issue": "2", "pages": "2100142"}, "abstract": "Asthma phenotyping requires novel biomarker discovery.\n\nTo identify plasma biomarkers associated with asthma phenotypes by application of a new proteomic panel to samples from two well-characterised cohorts of severe (SA) and mild-to-moderate (MMA) asthmatics, COPD subjects and healthy controls (HCs).\n\nAn antibody-based array targeting 177 proteins predominantly involved in pathways relevant to inflammation, lipid metabolism, signal transduction and extracellular matrix was applied to plasma from 525 asthmatics and HCs in the U-BIOPRED cohort, and 142 subjects with asthma and COPD from the validation cohort BIOAIR. Effects of oral corticosteroids (OCS) were determined by a 2-week, placebo-controlled OCS trial in BIOAIR, and confirmed by relation to objective OCS measures in U-BIOPRED.\n\nIn U-BIOPRED, 110 proteins were significantly different, mostly elevated, in SA compared to MMA and HCs. 10 proteins were elevated in SA versus MMA in both U-BIOPRED and BIOAIR (alpha-1-antichymotrypsin, apolipoprotein-E, complement component 9, complement factor I, macrophage inflammatory protein-3, interleukin-6, sphingomyelin phosphodiesterase 3, TNF receptor superfamily member 11a, transforming growth factor-\u03b2 and glutathione S-transferase). OCS treatment decreased most proteins, yet differences between SA and MMA remained following correction for OCS use. Consensus clustering of U-BIOPRED protein data yielded six clusters associated with asthma control, quality of life, blood neutrophils, high-sensitivity C-reactive protein and body mass index, but not Type-2 inflammatory biomarkers. The mast cell specific enzyme carboxypeptidase A3 was one major contributor to cluster differentiation.\n\nThe plasma proteomic panel revealed previously unexplored yet potentially useful Type-2-independent biomarkers and validated several proteins with established involvement in the pathophysiology of SA.", "doi": "10.1183/13993003.00142-2021", "pmid": "34737220", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Long-term Support WABI": "Collaborative", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC8850689"}, {"db": "pii", "key": "13993003.00142-2021"}], "notes": [], "created": "2021-11-10T10:57:08.791Z", "modified": "2024-01-16T13:48:37.618Z"}]}