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Calmangafodipir [Ca4Mn(DPDP)5], mangafodipir (MnDPDP) and MnPLED with special reference to their SOD mimetic and therapeutic properties
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
Department of Molecular and Medical Pharmacology, University of California, USA.
Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, Faculty of Science & Engineering.
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
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2015 (English)In: Drug Discovery Today, ISSN 1359-6446, E-ISSN 1878-5832, Vol. 20, no 4, 411-421 p.Article, review/survey (Refereed) Published
Abstract [en]

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) participate in pathological tissue damage. Mitochondrial manganese superoxide dismutase (MnSOD) normally keeps ROS and RNS in check. During development of mangafodipir (MnDPDP) as a magnetic resonance imaging (MRI) contrast agent, it was discovered that MnDPDP and its metabolite manganese pyridoxyl ethyldiamine (MnPLED) possessed SOD mimetic activity. MnDPDP has been tested as a chemotherapy adjunct in cancer patients and as an adjunct to percutaneous coronary intervention in patients with myocardial infarctions, with promising results. Whereas MRI contrast depends on release of Mn2+, the SOD mimetic activity depends on Mn2+ that remains bound to DPDP or PLED. Calmangafodipir [Ca4Mn(DPDP)5] is stabilized with respect to Mn2+ and has superior therapeutic activity. Ca4Mn(DPDP)5 is presently being explored as a chemotherapy adjunct in a clinical multicenter Phase II study in patients with metastatic colorectal cancer.

Place, publisher, year, edition, pages
Elsevier, 2015. Vol. 20, no 4, 411-421 p.
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Biochemistry and Molecular Biology
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URN: urn:nbn:se:liu:diva-118607DOI: 10.1016/j.drudis.2014.11.008ISI: 000354581300005PubMedID: 25463039OAI: oai:DiVA.org:liu-118607DiVA: diva2:817089
Available from: 2015-06-04 Created: 2015-06-02 Last updated: 2017-12-04Bibliographically approved

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Karlsson, Jan Olof GLundström, IngemarJynge, Per

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