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Calmangafodipir [Ca4Mn(DPDP)5], mangafodipir (MnDPDP) and MnPLED with special reference to their SOD mimetic and therapeutic properties.

Karlsson, Jan Olof G; Ignarro, Louis J; Lundström, Ingemar; Jynge, Per and Almén, Torsten LU (2015) In Drug Discovery Today 20(4). p.411-421
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.... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Drug Discovery Today
volume
20
issue
4
pages
411 - 421
publisher
Elsevier
external identifiers
  • pmid:25463039
  • wos:000354581300005
  • scopus:84928718985
ISSN
1878-5832
DOI
10.1016/j.drudis.2014.11.008
language
English
LU publication?
yes
id
3c027041-904b-41db-96eb-14a3afadbfb5 (old id 4912947)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25463039?dopt=Abstract
date added to LUP
2015-01-08 18:23:07
date last changed
2017-08-20 03:08:51
@article{3c027041-904b-41db-96eb-14a3afadbfb5,
  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.},
  author       = {Karlsson, Jan Olof G and Ignarro, Louis J and Lundström, Ingemar and Jynge, Per and Almén, Torsten},
  issn         = {1878-5832},
  language     = {eng},
  number       = {4},
  pages        = {411--421},
  publisher    = {Elsevier},
  series       = {Drug Discovery Today},
  title        = {Calmangafodipir [Ca4Mn(DPDP)5], mangafodipir (MnDPDP) and MnPLED with special reference to their SOD mimetic and therapeutic properties.},
  url          = {http://dx.doi.org/10.1016/j.drudis.2014.11.008},
  volume       = {20},
  year         = {2015},
}