{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:22:18Z","timestamp":1791278538511,"version":"4.1.0"},"reference-count":42,"publisher":"National Academy of Sciences","issue":"52","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,12,26]]},"abstract":"<jats:p>\n                    Furin plays a crucial role in embryogenesis and homeostasis and in diseases such as Alzheimer's disease, cancer, and viral and bacterial infections. Thus, inhibition of furin may provide a feasible and promising approach for therapeutic intervention of furin-mediated disease mechanisms. Here, we report on a class of small molecule furin inhibitors based on 2,5-dideoxystreptamine. Derivatization of 2,5-dideoxystreptamine by the addition of guanidinylated aryl groups yielded a set of furin inhibitors with nanomolar range potency against furin when assayed in a biochemical cleavage assay. Moreover, a subset of these furin inhibitors protected RAW 264.7 macrophage cells from toxicity caused by furin-dependent processing of anthrax protective antigen. These inhibitors were found to behave as competitive inhibitors of furin and to be relatively specific for furin. Molecular modeling revealed that these inhibitors may target the active site of furin as they showed site occupancy similar to the alkylating inhibitor decanoyl-Arg-Val-Lys-Arg-CH\n                    <jats:sub>2<\/jats:sub>\n                    Cl. The compounds presented here are bona fide synthetic small molecule furin inhibitors that exhibit potency in the nanomolar range, suggesting that they may serve as valuable tools for studying furin action and potential therapeutics agents for furin-dependent diseases.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0606555104","type":"journal-article","created":{"date-parts":[[2006,12,18]],"date-time":"2006-12-18T20:48:29Z","timestamp":1166474909000},"page":"19707-19712","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":81,"title":["Synthetic small molecule furin inhibitors derived from 2,5-dideoxystreptamine"],"prefix":"10.1073","volume":"103","author":[{"given":"Guan-Sheng","family":"Jiao","sequence":"first","affiliation":[{"name":"Departments of *Chemistry and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynne","family":"Cregar","sequence":"additional","affiliation":[{"name":"Lead Discovery, PanThera Biopharma LLC, 99-193 Aiea Heights Drive, Suite 136, Aiea, HI 96701; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinzhi","family":"Wang","sequence":"additional","affiliation":[{"name":"Vollum Institute, Oregon Health and Science University, Portland, OR 97239"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherri Z.","family":"Millis","sequence":"additional","affiliation":[{"name":"Lead Discovery, PanThera Biopharma LLC, 99-193 Aiea Heights Drive, Suite 136, Aiea, HI 96701; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cho","family":"Tang","sequence":"additional","affiliation":[{"name":"Departments of *Chemistry and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean","family":"O'Malley","sequence":"additional","affiliation":[{"name":"Departments of *Chemistry and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan T.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Departments of *Chemistry and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sina","family":"Sareth","sequence":"additional","affiliation":[{"name":"Departments of *Chemistry and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Larson","sequence":"additional","affiliation":[{"name":"Vollum Institute, Oregon Health and Science University, Portland, OR 97239"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Thomas","sequence":"additional","affiliation":[{"name":"Vollum Institute, Oregon Health and Science University, Portland, OR 97239"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2006,12,26]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3270625"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm934"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr010168i"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(98)01382-8"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.191199198"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.1.602-605.2004"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.12.7136-7139.2002"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.050504297"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.4.1851"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.8.5101-5105.2005"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0401406101"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2004.10.003"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.13.7293"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M102959200"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)82370-5"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3260507"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.9.3875-3882.2005"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(03)01393-0"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1032865100"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M003848200"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm00020a016"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi034418w"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj20030120"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2005.07.062"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3380107"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M400338200"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199909093411107"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/385833a0"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)42016-9"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1994.tb00500.x"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.79.10.3162"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(02)03609-8"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsb941"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2005.12.038"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.65.8.3370-3375.1997"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M400484200"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.26.1.354-361.2006"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/360358a0"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1139\/v78-065"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(73)90196-2"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.1999.1220"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(92)80300-6"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0606555104","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T15:30:59Z","timestamp":1649777459000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0606555104"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,12,26]]},"references-count":42,"journal-issue":{"issue":"52","published-print":{"date-parts":[[2006,12,26]]}},"alternative-id":["10.1073\/pnas.0606555104"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0606555104","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,12,26]]},"assertion":[{"value":"2006-07-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2006-12-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}