title: Calmangafodipir [Ca4Mn(DPDP)5], mangafodipir (MnDPDP) and MnPLED with special reference to their SOD mimetic and therapeutic properties.
abstract: 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 Mn(2+), the SOD mimetic activity depends on Mn(2+) that remains bound to DPDP or PLED. Calmangafodipir [Ca4Mn(DPDP)5] is stabilized with respect to Mn(2+) 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.
authors.affiliation: Division of Drug Research/Pharmacology, Linköping University, Linköping, Sweden. Electronic address: janolof.karlsson@ktias.com.
authors.forename: Jan Olof G
authors.initials: JO
authors.lastname: Karlsson
authors.affiliation: Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, USA.
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Ignarro
authors.affiliation: Department of Physics, Chemistry and Biology, Linköping University, Linköping, Sweden.
authors.forename: Ingemar
authors.initials: I
authors.lastname: Lundström
authors.affiliation: Division of Drug Research/Pharmacology, Linköping University, Linköping, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Jynge
authors.affiliation: Department of Diagnostic Radiology, Lund University, Malmö, Sweden.
authors.forename: Torsten
authors.initials: T
authors.lastname: Almén
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use*; D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D000067558:Biological Mimicry; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000473:pathology; D004492:Edetic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D005029:Ethylenediamines / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D006801:Humans; D008345:Manganese / Q000737:chemistry / Q000378:metabolism*; D015394:Molecular Structure; D009203:Myocardial Infarction / Q000628:therapy; D018384:Oxidative Stress / Q000187:drug effects; D062645:Percutaneous Coronary Intervention; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000378:metabolism; D013329:Structure-Activity Relationship; D013482:Superoxide Dismutase / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D005029:Ethylenediamines; D017382:Reactive Oxygen Species; D008345:Manganese; D011732:Pyridoxal Phosphate; C048753:N,N'-dipyridoxylethylenediamine-N,N'-diacetic acid; D004492:Edetic Acid; D013482:Superoxide Dismutase; C060076:N,N'-bis(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid