Department of Radiation Oncology, Duke University School of Medicine, Durham, NC 27710, USA.
Department of Obstetrics and Gynecology, Division of Reproductive Sciences, Duke Cancer Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Oxid Med Cell Longev. 2021 Mar 15;2021:6653790. doi: 10.1155/2021/6653790. eCollection 2021.
Mn(III) --alkyl- and -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, HO, HS, CO , 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-B and Nrf2), mitogen-activated protein kinases, MAPKs, antiapoptotic bcl-2, and endogenous antioxidative defenses. The lead Mn porphyrins, namely, MnTE-2-PyP (BMX-010, AEOL10113), MnTnBuOE-2-PyP (BMX-001), and MnTnHex-2-PyP, 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-PyP into four Phase II clinical trials on glioma, head and neck cancer, anal cancer, and multiple brain metastases, while MnTE-2-PyP is in Phase II clinical trial on atopic dermatitis and itch.
锰（III）-烷基-和-烷氧基烷基卟啉（MnPs）最初被开发为超氧化物歧化酶（SOD）模拟物。后来发现这些化合物与许多活性物质（如 ONOO、HO、HS、CO、抗坏血酸和 GSH）反应。此外，MnPs 氧化修饰许多蛋白质活性的能力已成为其在正常和癌细胞中的主要作用机制。这些蛋白质包括转录因子（NF-B 和 Nrf2）、丝裂原激活蛋白激酶（MAPKs）、MAPKs、抗凋亡 bcl-2 和内源性抗氧化防御。主要的锰卟啉，即 MnTE-2-PyP（BMX-010，AEOL10113）、MnTnBuOE-2-PyP（BMX-001）和 MnTnHex-2-PyP，已在正常组织和细胞以及动物癌症模型的多种损伤中进行了测试。大量的数据导致 MnTnBuOE-2-PyP 进入四项关于神经胶质瘤、头颈部癌症、肛门癌和多发性脑转移的 II 期临床试验，而 MnTE-2-PyP 则在特应性皮炎和瘙痒的 II 期临床试验中进行。
