Work

H2O2‐Driven Anticancer Activity of Mn Porphyrins and the Underlying Molecular Pathways

Year: 2021
Type: article
Abstract: Mn(III) ortho‐N‐alkyl‐ and N‐alkoxyalkyl porphyrins (MnPs) were initially developed as superoxide dismutase (SOD) mimics. These compounds were later shown to react with numerous reactive species (such as ONOO-, H2O2, H2S, CO3•-, ascorbate, and GSH). Moreover, the ability of MnPs to oxidatively modify activities of numerous proteins has emerged as their major mechanism of action both in normal and in cancer cells. Among those proteins are transcription factors (NF‐κB and Nrf2), mitogen‐activated protein kinases, MAPKs, antiapoptotic bcl‐2, and endogenous antioxidative defenses. The lead Mn porphyrins, namely, MnTE‐2‐PyP5+ (BMX‐010, AEOL10113), MnTnBuOE‐2‐PyP5+ (BMX‐001), and MnTnHex‐2‐PyP5+, were tested in numerous injuries of normal tissue and cellular and animal cancer models. The wealth of the data led to the progression of MnTnBuOE‐2‐PyP5+ into four Phase II clinical trials on glioma, head and neck cancer, anal cancer, and multiple brain metastases, while MnTE‐2‐PyP5+ is in Phase II clinical trial on atopic dermatitis and itch.
Language: English
Field: Medicine
Open Access status: hybrid
Estimated APC paid: $2,680
OpenAlex ID: W3139099677
FWCI: 6.077
Cites: 153
Cited by: 59
Related to: 10