{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T02:19:52Z","timestamp":1777861192166,"version":"3.51.4"},"reference-count":22,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T00:00:00Z","timestamp":1765324800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T00:00:00Z","timestamp":1765324800000},"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":[[2025,12,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Lakewood-Amedex Biotherapeutics Inc. has developed a new class of antimicrobials called the Bisphosphocin class, with Nu-3 as a leading candidate, which is currently in clinical development for treating mildly infected diabetic foot ulcers (iDFUs). Nu-3 acts through a novel mechanism of action that destabilizes bacterial membranes within minutes, which significantly reduces the potential for resistance development. It demonstrates broad-spectrum activity against Gram-positive, Gram-negative, and multidrug-resistant bacteria, including recent clinical isolates from infected wounds. Nu-3 is especially effective in acidic environments and can be formulated for topical application at high concentrations and low pH, that has been shown to be beneficial for wound healing, making it well-suited for treating infections in diabetic foot ulcers. Its rapid, bactericidal action has been confirmed against pathogens, such as\n                      <jats:italic toggle=\"yes\">Staphylococcus aureus<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Pseudomonas aeruginosa, Klebsiella pneumoniae, Propionibacterium acnes, Proteus mirabilis, Acinetobacter baumannii,<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Staphylococcus saprophyticus<\/jats:italic>\n                      , with complete bacterial eradication occurring within minutes. Resistance testing over 21 days showed a very low probability of resistance development.\n                      <jats:italic toggle=\"yes\">In vivo<\/jats:italic>\n                      testing in murine dermal methicillin-resistant\n                      <jats:italic toggle=\"yes\">Staphylococcus aureus<\/jats:italic>\n                      (MRSA) infection models demonstrated robust efficacy for Nu-3 given as a solution- or gel-formulation in both single and multidose protocols. Given its efficacy, broad-spectrum activity, and topical formulation, Nu-3 has the potential to be an important therapeutic intervention for the treatment of mild infections in diabetic foot ulcers\u2014a serious complication of diabetes associated with high amputation risk.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00948-25","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T17:13:48Z","timestamp":1761066828000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["<i>In vitro<\/i>\n                    and\n                    <i>in vivo<\/i>\n                    characterization of Bisphosphocin Nu-3\u2014a novel broad-spectrum antimicrobial compound with high potency against resistant pathogens"],"prefix":"10.1128","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3196-9194","authenticated-orcid":false,"given":"Kelvin","family":"Cooper","sequence":"first","affiliation":[{"name":"Lakewood-Amedex Biotherapeutics Inc.","place":["University Park, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kanneganti","family":"Murthy","sequence":"additional","affiliation":[{"name":"Lakewood-Amedex Biotherapeutics Inc.","place":["University Park, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Balzer","sequence":"additional","affiliation":[{"name":"Lakewood-Amedex Biotherapeutics Inc.","place":["University Park, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steve","family":"Parkinson","sequence":"additional","affiliation":[{"name":"Lakewood-Amedex Biotherapeutics Inc.","place":["University Park, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Randy","family":"Sleet","sequence":"additional","affiliation":[{"name":"Lakewood-Amedex Biotherapeutics Inc.","place":["University Park, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"DiTullio","sequence":"additional","affiliation":[{"name":"Lakewood-Amedex Biotherapeutics Inc.","place":["University Park, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)02724-0"},{"key":"e_1_3_3_3_2","volume-title":"Antibiotic resistance threats in the United States","author":"U.S. Department of Health and Human Services Center for Disease Control","year":"2019","unstructured":"U.S. Department of Health and Human Services Center for Disease Control. 2019. Antibiotic resistance threats in the United States"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1596\/26707"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa1581"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2021.747834"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cis34"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm8111935"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.656467"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1186\/1476-0711-10-1"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.2217\/fmb.15.70"},{"key":"e_1_3_3_12_2","volume-title":"Nu-3 is supplied as a disodium salt at >95% purity as characterized by 1H-,13C- and 35P-nmr, mass spectroscopy, and HPLC mass spec","year":"2018","unstructured":"2018. Nu-3 is supplied as a disodium salt at >95% purity as characterized by 1H-,13C- and 35P-nmr, mass spectroscopy, and HPLC mass spec"},{"key":"e_1_3_3_13_2","volume-title":"CLSI. Performance Standards for Antimicrobial Susceptibility Testing","author":"Clinical and Laboratory Standards Institute (CLSI)","year":"2018","unstructured":"Clinical and Laboratory Standards Institute (CLSI). 2018. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; Approved Standard\u2014Eleventh Edition. Clinical and Laboratory Standards Institute document M07. Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA. In CLSI. Performance Standards for Antimicrobial Susceptibility Testing, 32nd Ed. CLSI document M100, Wayne, Pennsylvania 19087, USA.","edition":"32"},{"key":"e_1_3_3_14_2","first-page":"257","article-title":"CPCSEA guidelines for laboratory animal facility","volume":"35","author":"Committee for the purpose of control and supervision on experiments on animals","year":"2003","unstructured":"Committee for the purpose of control and supervision on experiments on animals. 2003. CPCSEA guidelines for laboratory animal facility. Indian J Pharmacol 35:257\u2013274.","journal-title":"Indian J Pharmacol"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid2111.150452"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cis346"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.21.5.855"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.24.1.84"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0177916"},{"key":"e_1_3_3_20_2","volume-title":"International Working Group on the Diabetic Foot (IWGDF) guidance on the diagnosis and management of foot infections in persons with diabetes","author":"Lipsky BA","year":"2016","unstructured":"Lipsky BA, Arag\u00f3n-S\u00e1nchez J, Diggle M, Embil J, Kono S, Lavery L, Senneville E, Urbancic-Rovan V, Asten S, Peters EJG. 2016. International Working Group on the Diabetic Foot (IWGDF) guidance on the diagnosis and management of foot infections in persons with diabetes"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciad527"},{"key":"e_1_3_3_22_2","volume-title":"Novel Bisphosphocin Nu-3 demonstrates rapid killing of bacteria-encased in biofilm in vitro, 2013, 53rd","author":"Akiyoshi D","year":"2013","unstructured":"Akiyoshi D, Dilo J, DiTullio P. 2013. Novel Bisphosphocin Nu-3 demonstrates rapid killing of bacteria-encased in biofilm in vitro, 2013, 53rd. 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