{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T16:57:15Z","timestamp":1790096235066,"version":"4.0.1"},"reference-count":12,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2015,10,13]],"date-time":"2015-10-13T00:00:00Z","timestamp":1444694400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2015,11,1]],"date-time":"2015-11-01T00:00:00Z","timestamp":1446336000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            A series of novel tetracycline derivatives were synthesized with the goal of creating new antibiotics that would be unaffected by the known tetracycline resistance mechanisms. New C-9-position derivatives of minocycline (the aminomethylcyclines [AMCs]) were tested for\n            <jats:italic>in vitro<\/jats:italic>\n            activity against Gram-positive strains containing known tetracycline resistance mechanisms of ribosomal protection (Tet M in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Staphylococcus aureus<\/jats:named-content>\n            ,\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Enterococcus faecalis<\/jats:named-content>\n            , and\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Streptococcus pneumoniae<\/jats:named-content>\n            ) and efflux (Tet K in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. aureus<\/jats:named-content>\n            and Tet L in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. faecalis<\/jats:named-content>\n            ). A number of aminomethylcyclines with potent\n            <jats:italic>in vitro<\/jats:italic>\n            activity (MIC range of \u22640.06 to 2.0 \u03bcg\/ml) were identified. These novel tetracyclines were more active against one or more of the resistant strains than the reference antibiotics tested (MIC range, 16 to 64 \u03bcg\/ml). The AMC derivatives were active against bacteria resistant to tetracycline by both efflux and ribosomal protection mechanisms. This study identified the AMCs as a novel class of antibiotics evolved from tetracycline that exhibit potent activity\n            <jats:italic>in vitro<\/jats:italic>\n            against tetracycline-resistant Gram-positive bacteria, including pathogenic strains of methicillin-resistant\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. aureus<\/jats:named-content>\n            (MRSA) and vancomycin-resistant enterococci (VRE). One derivative, 9-neopentylaminomethylminocycline (generic name omadacycline), was identified and is currently in human trials for acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP).\n          <\/jats:p>","DOI":"10.1128\/aac.01536-15","type":"journal-article","created":{"date-parts":[[2015,9,9]],"date-time":"2015-09-09T02:21:18Z","timestamp":1441765278000},"page":"7044-7053","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":128,"title":["Structure-Activity Relationship of the Aminomethylcyclines and the Discovery of Omadacycline"],"prefix":"10.1128","volume":"59","author":[{"given":"Laura","family":"Honeyman","sequence":"first","affiliation":[{"name":"Paratek Pharmaceuticals, Inc., Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Ismail","sequence":"additional","affiliation":[{"name":"Paratek Pharmaceuticals, Inc., Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark L.","family":"Nelson","sequence":"additional","affiliation":[{"name":"Paratek Pharmaceuticals, Inc., Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beena","family":"Bhatia","sequence":"additional","affiliation":[{"name":"Paratek Pharmaceuticals, Inc., Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd E.","family":"Bowser","sequence":"additional","affiliation":[{"name":"Paratek Pharmaceuticals, Inc., Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jackson","family":"Chen","sequence":"additional","affiliation":[{"name":"Paratek Pharmaceuticals, Inc., Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachid","family":"Mechiche","sequence":"additional","affiliation":[{"name":"Paratek Pharmaceuticals, Inc., Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwasi","family":"Ohemeng","sequence":"additional","affiliation":[{"name":"Paratek Pharmaceuticals, Inc., Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atul K.","family":"Verma","sequence":"additional","affiliation":[{"name":"Paratek Pharmaceuticals, Inc., Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. Pat","family":"Cannon","sequence":"additional","affiliation":[{"name":"Paratek Pharmaceuticals, Inc., Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Macone","sequence":"additional","affiliation":[{"name":"Paratek Pharmaceuticals, Inc., Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Ken","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Paratek Pharmaceuticals, Inc., Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart","family":"Levy","sequence":"additional","affiliation":[{"name":"Paratek Pharmaceuticals, Inc., Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2011.06354.x"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-009-0172-6"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4892(01)00081-9"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dki248"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200565100-00002"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo030047d"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01066-13"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01242-13"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00948-12"},{"key":"e_1_3_2_11_2","volume-title":"Clinical and Laboratory Standards Institute document M7-A7","author":"Clinical and Laboratory Standards Institute","year":"2006","unstructured":"Clinical and Laboratory Standards Institute. 2006. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard\u20147th ed. Clinical and Laboratory Standards Institute document M7-A7. Clinical and Laboratory Standards Institute, Wayne, PA."},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(94)90396-4"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02036-13"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01536-15","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01536-15","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T22:39:57Z","timestamp":1645483197000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.01536-15"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,11]]},"references-count":12,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2015,11]]}},"alternative-id":["10.1128\/AAC.01536-15"],"URL":"https:\/\/doi.org\/10.1128\/aac.01536-15","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,11]]},"assertion":[{"value":"2015-07-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-08-31","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-10-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}