{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T02:16:09Z","timestamp":1793067369423,"version":"4.5.0"},"reference-count":200,"publisher":"SAGE Publications","issue":"16","license":[{"start":{"date-parts":[[2018,10,17]],"date-time":"2018-10-17T00:00:00Z","timestamp":1539734400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:sec>\n                    <jats:title>Significance:<\/jats:title>\n                    <jats:p>\n                      After approximatelty three decades of research, two Mn(III) porphyrins (MnPs), MnTE-2-PyP\n                      <jats:sup>5+<\/jats:sup>\n                      (BMX-010, AEOL10113) and MnTnBuOE-2-PyP\n                      <jats:sup>5+<\/jats:sup>\n                      (BMX-001), have progressed to five clinical trials. In parallel, another similarly potent metal-based superoxide dismutase (SOD) mimic\u2014Mn(II)pentaaza macrocycle, GC4419\u2014has been tested in clinical trial on application, identical to that of MnTnBuOE-2-PyP\n                      <jats:sup>5+<\/jats:sup>\n                      \u2014radioprotection of normal tissue in head and neck cancer patients. This clearly indicates that Mn complexes that target cellular redox environment have reached sufficient maturity for clinical applications.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Recent Advances:<\/jats:title>\n                    <jats:p>\n                      While originally developed as SOD mimics, MnPs undergo intricate interactions with numerous redox-sensitive pathways, such as those involving nuclear factor \u03baB (NF-\u03baB) and nuclear factor E2-related factor 2 (Nrf2), thereby impacting cellular transcriptional activity. An increasing amount of data support the notion that MnP\/H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      \/glutathione (GSH)-driven catalysis of\n                      <jats:italic toggle=\"yes\">S<\/jats:italic>\n                      -glutathionylation of protein cysteine, associated with modification of protein function, is a major action of MnPs on molecular level.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Critical Issues:<\/jats:title>\n                    <jats:p>\n                      Differential effects of MnPs on normal\n                      <jats:italic toggle=\"yes\">versus<\/jats:italic>\n                      tumor cells\/tissues, which support their translation into clinic, arise from differences in their accumulation and redox environment of such tissues. This in turn results in different yields of MnP-driven modifications of proteins. Thus far, direct evidence for such modification of NF-\u03baB, mitogen-activated protein kinases (MAPK), phosphatases, Nrf2, and endogenous antioxidative defenses was provided in tumor, while indirect evidence shows the modification of NF-\u03baB and Nrf2 translational activities by MnPs in normal tissue.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Future Directions:<\/jats:title>\n                    <jats:p>Studies that simultaneously explore differential effects in same animal are lacking, while they are essential for understanding of extremely intricate interactions of metal-based drugs with complex cellular networks of normal and cancer cells\/tissues.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/ars.2017.7453","type":"journal-article","created":{"date-parts":[[2018,6,21]],"date-time":"2018-06-21T07:04:29Z","timestamp":1529564669000},"page":"1691-1724","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":148,"title":["Mn Porphyrin-Based Redox-Active Drugs: Differential Effects as Cancer Therapeutics and Protectors of Normal Tissue Against Oxidative Injury"],"prefix":"10.1177","volume":"29","author":[{"given":"Ines","family":"Batinic-Haberle","sequence":"first","affiliation":[{"name":"Duke University School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Artak","family":"Tovmasyan","sequence":"additional","affiliation":[{"name":"Duke University School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Spasojevic","sequence":"additional","affiliation":[{"name":"Duke University School of Medicine"},{"name":"Duke Cancer Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2018,10,17]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pdpdt.2016.11.009"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2013.09.005"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2012.10.099"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.34.15_suppl.10120"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2017.10.019"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.117.007861"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2013.10.002"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2015.07.2283"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-30705-3_19"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2011.407"},{"key":"e_1_3_2_12_2","first-page":"169","article-title":"HIF-1alpha restricts NF-kappaB-dependent gene expression to control innate immunity signals","volume":"8","author":"Bandarra D","year":"2015","unstructured":"Bandarra D, , Biddlestone J, , Mudie S, , Muller HA, , and Rocha S. 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