{"entity": "researcher", "timestamp": "2026-08-22T06:58:23.634Z", "family": "Giacomini", "given": "Kathleen M", "initials": "KM", "orcid": "0000-0001-8041-5430", "affiliations": ["Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA. kathy.giacomini@ucsf.edu."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/c21870e6486645a092bd068497570f32.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/c21870e6486645a092bd068497570f32"}}, "publications": [{"entity": "publication", "iuid": "e535c0bd82904343b97f99b3c5d212ed", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/e535c0bd82904343b97f99b3c5d212ed.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/e535c0bd82904343b97f99b3c5d212ed"}}, "title": "Illuminating the function of the orphan transporter, SLC22A10, in humans and other primates.", "authors": [{"family": "Yee", "given": "Sook Wah", "initials": "SW", "orcid": "0000-0001-8121-8746", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/edc914fd29504965bba2bbe7e3286591.json"}}, {"family": "Ferr\u00e1ndez-Peral", "given": "Luis", "initials": "L", "orcid": "0000-0003-0338-0603", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d338573c126e437e91d1103d37f07d92.json"}}, {"family": "Alentorn-Moron", "given": "Pol", "initials": "P", "orcid": "0000-0002-4858-0652", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b34176e564cf4a33a29b7b5d5441d1f5.json"}}, {"family": "Fontsere", "given": "Claudia", "initials": "C", "orcid": "0000-0003-2233-6026", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f9629b2d83194a1aa43ca4b838db5e87.json"}}, {"family": "Ceylan", "given": "Merve", "initials": "M", "orcid": "0000-0003-4252-6329", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/06b38fdd16f9411fb0305f1bd0bda78a.json"}}, {"family": "Koleske", "given": "Megan L", "initials": "ML"}, {"family": "Handin", "given": "Niklas", "initials": "N"}, {"family": "Artegoitia", "given": "Virginia M", "initials": "VM"}, {"family": "Lara", "given": "Giovanni", "initials": "G", "orcid": "0009-0004-6706-0945", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/239a14bab1534924a0d29396d82ae91c.json"}}, {"family": "Chien", "given": "Huan-Chieh", "initials": "HC"}, {"family": "Zhou", "given": "Xujia", "initials": "X"}, {"family": "Dainat", "given": "Jacques", "initials": "J", "orcid": "0000-0002-6629-0173", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ebbfdb5bd1ae4faf83550da6c0168fcb.json"}}, {"family": "Zalevsky", "given": "Arthur", "initials": "A", "orcid": "0000-0001-6987-8119", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7fdb6c4d5c9b4feb83952a3674708a12.json"}}, {"family": "Sali", "given": "Andrej", "initials": "A", "orcid": "0000-0003-0435-6197", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/dd70ba581f7e49b886339e8883b7f053.json"}}, {"family": "Brand", "given": "Colin M", "initials": "CM"}, {"family": "Wolfreys", "given": "Finn D", "initials": "FD"}, {"family": "Yang", "given": "Jia", "initials": "J", "orcid": "0000-0002-3992-4070", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ef96e625276f4b92a49be676bdb5a191.json"}}, {"family": "Gestwicki", "given": "Jason E", "initials": "JE", "orcid": "0000-0002-6125-3154", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/08100243ce874cf7888220b24267131b.json"}}, {"family": "Capra", "given": "John A", "initials": "JA", "orcid": "0000-0001-9743-1795", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/043f7e6a813c4385b53e67fe715e27ce.json"}}, {"family": "Artursson", "given": "Per", "initials": "P", "orcid": "0000-0002-3708-7395", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9908209a413a4088b6bf44a924d27319.json"}}, {"family": "Newman", "given": "John W", "initials": "JW", "orcid": "0000-0001-9632-6571", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/54a84a77486644ce8cb2bc1ac34c81dd.json"}}, {"family": "Marqu\u00e8s-Bonet", "given": "Tom\u00e0s", "initials": "T", "orcid": "0000-0002-5597-3075", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1091cb5bfe394d459969d24bb1c22c66.json"}}, {"family": "Giacomini", "given": "Kathleen M", "initials": "KM", "orcid": "0000-0001-8041-5430", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c21870e6486645a092bd068497570f32.json"}}], "type": "journal article", "published": "2024-05-23", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "15", "issue": "1", "pages": "4380", "issn-l": "2041-1723"}, "abstract": "SLC22A10 is an orphan transporter with unknown substrates and function. The goal of this study is to elucidate its substrate specificity and functional characteristics. In contrast to orthologs from great apes, human SLC22A10, tagged with green fluorescent protein, is not expressed on the plasma membrane. Cells expressing great ape SLC22A10 orthologs exhibit significant accumulation of estradiol-17\u03b2-glucuronide, unlike those expressing human SLC22A10. Sequence alignments reveal a proline at position 220 in humans, which is a leucine in great apes. Replacing proline with leucine in SLC22A10-P220L restores plasma membrane localization and uptake function. Neanderthal and Denisovan genomes show proline at position 220, akin to modern humans, indicating functional loss during hominin evolution. Human SLC22A10 is a unitary pseudogene due to a fixed missense mutation, P220, while in great apes, its orthologs transport sex steroid conjugates. Characterizing SLC22A10 across species sheds light on its biological role, influencing organism development and steroid homeostasis.", "doi": "10.1038/s41467-024-48569-7", "pmid": "38782905", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11116522"}, {"db": "pii", "key": "10.1038/s41467-024-48569-7"}], "notes": [], "created": "2026-08-21T11:49:47.470Z", "modified": "2026-08-21T11:49:48.071Z"}, {"entity": "publication", "iuid": "ecb3461dd9784f82b3d06354e557a641", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/ecb3461dd9784f82b3d06354e557a641.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/ecb3461dd9784f82b3d06354e557a641"}}, "title": "High Throughput Screening of a Prescription Drug Library for Inhibitors of Organic Cation Transporter 3, OCT3.", "authors": [{"family": "Chen", "given": "Eugene C", "initials": "EC"}, {"family": "Matsson", "given": "P\u00e4r", "initials": "P"}, {"family": "Azimi", "given": "Mina", "initials": "M"}, {"family": "Zhou", "given": "Xujia", "initials": "X"}, {"family": "Handin", "given": "Niklas", "initials": "N"}, {"family": "Yee", "given": "Sook Wah", "initials": "SW"}, {"family": "Artursson", "given": "Per", "initials": "P"}, {"family": "Giacomini", "given": "Kathleen M", "initials": "KM", "orcid": "0000-0001-8041-5430", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c21870e6486645a092bd068497570f32.json"}}], "type": "journal article", "published": "2022-07-00", "journal": {"title": "Pharm. Res.", "issn": "1573-904X", "volume": "39", "issue": "7", "pages": "1599-1613", "issn-l": "0724-8741"}, "abstract": "The organic cation transporter 3 (OCT3, SLC22A3) is ubiquitously expressed and interacts with a wide array of compounds including endogenous molecules, environmental toxins and prescription drugs. Understudied as a determinant of pharmacokinetics and pharmacodynamics, OCT3 has the potential to be a major determinant of drug absorption and disposition and to be a target for drug-drug interactions (DDIs).\n\nThe goal of the current study was to identify prescription drug inhibitors of OCT3.\n\nWe screened a compound library consisting of 2556 prescription drugs, bioactive molecules, and natural products using a high throughput assay in HEK-293 cells stably expressing OCT3.\n\nWe identified 210 compounds that at 20 \u03bcM inhibit 50% or more of OCT3-mediated uptake of 4-Di-1-ASP (2 \u03bcM). Of these, nine were predicted to inhibit the transporter at clinically relevant unbound plasma concentrations. A Structure-Activity Relationship (SAR) model included molecular descriptors that could discriminate between inhibitors and non-inhibitors of OCT3 and was used to identify additional OCT3 inhibitors. Proteomics of human brain microvessels (BMVs) indicated that OCT3 is the highest expressed OCT in the human blood-brain barrier (BBB).\n\nThis study represents the largest screen to identify prescription drug inhibitors of OCT3. Several are sufficiently potent to inhibit the transporter at therapeutic unbound plasma levels, potentially leading to DDIs or off-target pharmacologic effects.", "doi": "10.1007/s11095-022-03171-8", "pmid": "35089508", "labels": [], "xrefs": [{"db": "mid", "key": "NIHMS1799969"}, {"db": "pmc", "key": "PMC9246766"}, {"db": "pii", "key": "10.1007/s11095-022-03171-8"}], "notes": [], "created": "2026-08-20T06:40:17.865Z", "modified": "2026-08-20T06:40:17.966Z"}]}