Mn Porphyrin-Based Redox-Active Therapeutics

Nitroxidative Signaling Mechanisms in Pathological Pain

“…These processes can cause peripheral and central sensitization, which underlie pathological pain (see Glossary) [5,6]. Thus, restoring nitroxidative balance in peripheral and central nervous systems (PNS, CNS) is a possible therapeutic approach for ameliorating neuropathology [6–10]. …”

“…The consensus view is that the possible beneficial effects are outweighed by unfavorable pharmacokinetic and pharmacodynamic profiles [13,178,179]. A variety of redox-active therapeutics are being developed to overcome these issues and are effective in in treating cancer-induced bone pain, inflammatory, and neuropathic pain, and can also potentiate opioid analgesia [9,10,180]. …”

Update on hypoxia-inducible factors and hydroxylases in oxygen regulatory pathways: from physiology to therapeutics

“…The magnitude of all actions of MnPs thus far studied, including SOD-like activity, parallels the magnitude of their therapeutic efficacies and is dependent upon the metal-centered reduction potential of Mn III P/Mn II P redox couple; in turn the magnitude of those actions parallels each other. In addition to reacting with different RS, MnPs inhibit activities of several transcription factors, such as HIF-1α, NF-κB, AP-1, SP-1, and Nrf2, thereby affecting cellular apoptotic and proliferative pathways 64–66. The nature of such interactions has mostly been explored with respect to NF-κB and has been ascribed to MnP-catalyzed and H 2 O 2 /GSH-driven oxidation/ S -glutathionylation of thiols in its p50 and p65 subunits.…”

“…MnPs exhibit differential effects to normal and tumor tissues presumably by impacting NFκB/HIF-1α/Nrf2 pathways 64–66. The HIF and NF-κB pathways are closely related.…”

“…This is due to its perturbed redox environment, often with increased MnSOD levels but insufficient levels and/or activities of peroxide-removing enzymes 64–66. Such situation has been heavily exploited in anticancer therapies, one of which includes MnP alone and/or combined with exogenously imposed oxidative stress.…”