{"entity": "researcher", "timestamp": "2026-11-06T20:05:32.045Z", "family": "Korabecny", "given": "Jan", "initials": "J", "orcid": "0000-0001-6977-7596", "affiliations": ["Biomedical Research Centre, University Hospital Hradec Kr\u00e1lov\u00e9, Sokolsk\u00e1 581, 500 05 Hradec Kr\u00e1lov\u00e9, Czech Republic."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/5d8ccabb54834566ac9e298119a28484.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/5d8ccabb54834566ac9e298119a28484"}}, "publications": [{"entity": "publication", "iuid": "0b81a745fadc4c0290088434d799cfe1", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/0b81a745fadc4c0290088434d799cfe1.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/0b81a745fadc4c0290088434d799cfe1"}}, "title": "Rare genetic variability in human drug target genes modulates drug response and can guide precision medicine.", "authors": [{"family": "Zhou", "given": "Yitian", "initials": "Y", "orcid": "0000-0003-3066-5444", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c4e92db79d554ad283927ad7e6e54e8d.json"}}, {"family": "Arribas", "given": "Gabriel Herras", "initials": "GH", "orcid": "0000-0001-8067-7764", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c7a40eec7f3640d5923fca506e379c3c.json"}}, {"family": "Turku", "given": "Ainoleena", "initials": "A", "orcid": "0000-0003-0959-7221", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/80fbb027505240eaaebf4153df67a47f.json"}}, {"family": "J\u00fcrgenson", "given": "Tuuli", "initials": "T"}, {"family": "Mkrtchian", "given": "Souren", "initials": "S", "orcid": "0000-0001-9801-2736", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4f0178b0c4ad4bfab16b512fce21b119.json"}}, {"family": "Krebs", "given": "Kristi", "initials": "K", "orcid": "0000-0003-0494-2751", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1b98e04677d64206a83cab1c1328d936.json"}}, {"family": "Wang", "given": "Yi", "initials": "Y", "orcid": "0000-0002-3676-9183", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a03091d5222a409ba70c5fe26ac5455f.json"}}, {"family": "Svobodova", "given": "Barbora", "initials": "B", "orcid": "0000-0001-8099-089X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c58cb8dce631456d8a500ba4193c8b84.json"}}, {"family": "Milani", "given": "Lili", "initials": "L", "orcid": "0000-0002-5323-3102", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e92d1400307a42f3a8baffc008996d1b.json"}}, {"family": "Schulte", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-2700-7013", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5ca48082cc934a8494ac50e756be0f3e.json"}}, {"family": "Korabecny", "given": "Jan", "initials": "J", "orcid": "0000-0001-6977-7596", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5d8ccabb54834566ac9e298119a28484.json"}}, {"family": "Gastaldello", "given": "Stefano", "initials": "S", "orcid": "0000-0001-7369-8452", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ad2f016a7270481b8085475e22441815.json"}}, {"family": "Lauschke", "given": "Volker M", "initials": "VM", "orcid": "0000-0002-1140-6204", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/82048d4da61547d08aa9d2bb3bae12dd.json"}}], "type": "journal article", "published": "2021-09-03", "journal": {"title": "Sci Adv", "issn": "2375-2548", "volume": "7", "issue": "36", "pages": "eabi6856", "issn-l": "2375-2548"}, "abstract": "Interindividual variability in drug response constitutes a major concern in pharmacotherapy. While polymorphisms in genes involved in drug disposition have been extensively studied, drug target variability remains underappreciated. By mapping the genomic variability of all human drug target genes onto high-resolution crystal structures of drug target complexes, we identified 1094 variants localized within 6 \u00c5 of drug-binding pockets and directly affecting their geometry, topology, or physicochemical properties. We experimentally show that binding site variants affect pharmacodynamics with marked drug- and variant-specific differences. In addition, we demonstrate that a common BCHE variant confers resistance to tacrine and rivastigmine, which can be overcome by the use of derivatives based on squaric acid scaffolds or tryptophan conjugation. These findings underscore the importance of genetic drug target variability and demonstrate that integration of genomic data and structural information can inform personalized drug selection and genetically guided drug development to overcome resistance.", "doi": "10.1126/sciadv.abi6856", "pmid": "34516913", "labels": {"DDLS Fellow": null, "Yitian Zhou": null}, "xrefs": [{"db": "pmc", "key": "PMC8442892"}], "notes": [], "created": "2026-11-06T09:27:07.941Z", "modified": "2026-11-06T09:27:08.312Z"}, {"entity": "publication", "iuid": "96feeff56c5b42afa3e471fcdf5edecb", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/96feeff56c5b42afa3e471fcdf5edecb.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/96feeff56c5b42afa3e471fcdf5edecb"}}, "title": "Exploring Structure-Activity Relationship in Tacrine-Squaramide Derivatives as Potent Cholinesterase Inhibitors.", "authors": [{"family": "Svobodova", "given": "Barbora", "initials": "B"}, {"family": "Mezeiova", "given": "Eva", "initials": "E"}, {"family": "Hepnarova", "given": "Vendula", "initials": "V", "orcid": "0000-0002-6445-2669", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/097e96286b684387929600c1eff9286c.json"}}, {"family": "Hrabinova", "given": "Martina", "initials": "M", "orcid": "0000-0002-9428-4109", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/13d23c19b3734174a006f267ab0370a5.json"}}, {"family": "Muckova", "given": "Lubica", "initials": "L", "orcid": "0000-0001-6693-6061", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c8b59f0ac5714bbbb50d156411e635f4.json"}}, {"family": "Kobrlova", "given": "Tereza", "initials": "T", "orcid": "0000-0002-4445-0287", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3ff3f52010234a469ea38749877400d4.json"}}, {"family": "Jun", "given": "Daniel", "initials": "D", "orcid": "0000-0002-0882-6304", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2b57345825864df990ab1dfbbaeaabc7.json"}}, {"family": "Soukup", "given": "Ondrej", "initials": "O"}, {"family": "Jimeno", "given": "Mar\u00eda Luisa", "initials": "ML"}, {"family": "Marco-Contelles", "given": "Jos\u00e9", "initials": "J"}, {"family": "Korabecny", "given": "Jan", "initials": "J", "orcid": "0000-0001-6977-7596", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5d8ccabb54834566ac9e298119a28484.json"}}], "type": "journal article", "published": "2019-08-19", "journal": {"title": "Biomolecules", "issn": "2218-273X", "volume": "9", "issue": "8", "issn-l": null}, "abstract": "Tacrine was the first drug to be approved for Alzheimer's disease (AD) treatment, acting as a cholinesterase inhibitor. The neuropathological hallmarks of AD are amyloid-rich senile plaques, neurofibrillary tangles, and neuronal degeneration. The portfolio of currently approved drugs for AD includes acetylcholinesterase inhibitors (AChEIs) and N-methyl-d-aspartate (NMDA) receptor antagonist. Squaric acid is a versatile structural scaffold capable to be easily transformed into amide-bearing compounds that feature both hydrogen bond donor and acceptor groups with the possibility to create multiple interactions with complementary sites. Considering the relatively simple synthesis approach and other interesting properties (rigidity, aromatic character, H-bond formation) of squaramide motif, we combined this scaffold with different tacrine-based derivatives. In this study, we developed 21 novel dimers amalgamating squaric acid with either tacrine, 6-chlorotacrine or 7-methoxytacrine representing various AChEIs. All new derivatives were evaluated for their anti-cholinesterase activities, cytotoxicity using HepG2 cell line and screened to predict their ability to cross the blood-brain barrier. In this contribution, we also report in silico studies of the most potent AChE and BChE inhibitors in the active site of these enzymes.", "doi": "10.3390/biom9080379", "pmid": "31430943", "labels": {"DDLS Fellow": null, "Yitian Zhou": null}, "xrefs": [{"db": "pmc", "key": "PMC6723352"}, {"db": "pii", "key": "biom9080379"}], "notes": [], "created": "2026-11-06T09:29:48.258Z", "modified": "2026-11-06T09:29:48.604Z"}]}