{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T06:54:12Z","timestamp":1781592852778,"version":"3.54.5"},"reference-count":52,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T00:00:00Z","timestamp":1780790400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T00:00:00Z","timestamp":1780790400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB1552 \u2010 \u201cDefects and Defect engineering in Soft Matter,\u201d project number 465145163"],"award-info":[{"award-number":["SFB1552 \u2010 \u201cDefects and Defect engineering in Soft Matter,\u201d project number 465145163"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemBioChem"],"published-print":{"date-parts":[[2026,6,15]]},"abstract":"<jats:p>\n                    Drug uptake is constrained by epithelial barriers, such as the intestine and the blood\u2013brain barrier, which express efflux pumps such as the ABC\u2010transporter ABCB1. Therefore, drugs targeting the central nervous system frequently require co\u2010administration of efflux inhibitors to facilitate sufficient target engagement. Conversely, certain drugs designed to target distinct molecular pathways may inadvertently affect ABC transporters. However, detailed functional studies of putative human ABCB1 inhibitors is challenging due to difficulties in obtaining sufficiently high amounts of protein needed. Bacterial ABC transporters, such as BmrA from\n                    <jats:italic>Bacillus subtilis<\/jats:italic>\n                    , share structural and functional similarities with ABCB1 and thus provide a reasonable alternative model system. This study investigates clomipramine, an antidepressant known to reduce multidrug resistance in human cells by a yet undefined mechanism. We demonstrate that clomipramine inhibits the ATPase activity of both full\u2010length BmrA and its isolated nucleotide\u2010binding domain. Using binding assays and molecular modeling, multiple clomipramine binding sites were identified in BmrA, which are also conserved in human ABCB1. Critically, one predicted site overlaps with the ATP\u2010binding pocket. The results underscore the potential side\u2010effects of clomipramine and highlight the value of bacterial models such as BmrA for studying novel inhibitors when studies on human proteins are not feasible.\n                  <\/jats:p>","DOI":"10.1002\/cbic.202500937","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T06:15:09Z","timestamp":1780899309000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Antidepressant Drug Clomipramine Inhibits the ABC Transporter BmrA"],"prefix":"10.1002","volume":"27","author":[{"given":"Nadja","family":"Hellmann","sequence":"first","affiliation":[{"name":"Department of Chemistry \u2010 Biochemistry Johannes Gutenberg University Mainz  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Kersten","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical and Biomedical Sciences \u2010 Medical Chemistry Johannes Gutenberg\u2010University Mainz  Germany"},{"name":"Institute for Quantitative and Computational Biosciences Johannes Gutenberg\u2010University Mainz  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Efferth","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical and Biomedical Sciences \u2010 Pharmaceutical Biology Johannes Gutenberg University Mainz  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4517-6387","authenticated-orcid":false,"given":"Dirk","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department of Chemistry \u2010 Biochemistry Johannes Gutenberg University Mainz  Germany"},{"name":"Institute of Molecular Physiology Johannes Gutenberg University Mainz  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,7]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/PL00006442"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.201411164"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.13935"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-019-0390-x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0709388104"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1204067109"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep41575"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2008.0125"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-65037-y"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2024.107440"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-018-0048-6"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05155"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2024.101609"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-409X(02)00169-2"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0325121"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1039\/D3MD00612C"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1039\/D3MD00649B"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph16020205"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-48281-4"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.00001-07"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/34669"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi0362018"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24065239"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222413565"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2025.184430"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1177\/0897190014521996"},{"key":"e_1_2_9_28_1","unstructured":"M.WilsonandJ.Tripp Clomipramine. StatPearls Publishing https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK541006\/\/ Assessed 17.05.26."},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12648"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2005-916184"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvp.12111"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3565(24)39030-5"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/0277-5379(91)90054-H"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1461145713000692"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi702303s"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20051719"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1021\/ci6002202"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12104-021-10063-2"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M210413200"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.1999.1375"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/jb\/mvad038"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1097\/00002826-198503000-00008"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0327(93)90017-E"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1177\/089198879400700302"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.2c08273"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2020.104452"},{"key":"e_1_2_9_47_1","first-page":"2022","article-title":"Substrate\u2010Bound and Substrate\u2010Free Outward\u2010Facing Structures of a Multidrug ABC Exporter","volume":"8","author":"Chaptal V.","journal-title":"Science Advances"},{"key":"e_1_2_9_48_1","first-page":"2025","article-title":"Rhodamine6G and H\u0153chst33342 Narrow BmrA Conformational Spectrum for a More Efficient use of ATP","volume":"16","author":"Gobet A.","year":"1745","journal-title":"Nature Communications"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.235"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aar7389"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-58561-4"},{"key":"e_1_2_9_52_1","volume-title":"Molecular Operating Environment (MOE)","author":"Chemical Computing Group ULC","year":"2021"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20933"}],"container-title":["ChemBioChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbic.202500937","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cbic.202500937","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbic.202500937","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T06:20:35Z","timestamp":1781590835000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cbic.202500937"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,7]]},"references-count":52,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2026,6,15]]}},"alternative-id":["10.1002\/cbic.202500937"],"URL":"https:\/\/doi.org\/10.1002\/cbic.202500937","archive":["Portico"],"relation":{},"ISSN":["1439-4227","1439-7633"],"issn-type":[{"value":"1439-4227","type":"print"},{"value":"1439-7633","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,7]]},"assertion":[{"value":"2025-11-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e202500937"}}