Ball Patrick, Hobbs Robert, Anderson Simon, Thompson Emma, Gwenin Vanessa, Von Ruhland Christopher, Gwenin Christopher
School of Natural Sciences, Bangor University, Bangor, Gwynedd, Wales LL57 2UW, UK.
College of Biomedical and Life Sciences, Cardiff University, Cardiff CF14 4XN, UK.
Pharmaceutics. 2021 Apr 9;13(4):517. doi: 10.3390/pharmaceutics13040517.
The bacterial nitroreductase NfnB has been the focus of a great deal of research for its use in directed enzyme prodrug therapy in combination with the nitroreductase prodrug CB1954 with this combination of enzyme and prodrug even entering clinical trials. Despite some promising results, there are major limitations to this research, such as the fact that the lowest reported Km for this enzyme far exceeds the maximum dosage of CB1954. Due to these limitations, new enzymes are now being investigated for their potential use in directed enzyme prodrug therapy. One such enzyme that has proved promising is the YfkO nitroreductase from Bacillus Licheniformis. Upon investigation, the YfkO nitroreductase was shown to have a much lower Km (below the maximum dosage) than that of NfnB as well as the fact that when reacting with the prodrug it produces a much more favourable ratio of enzymatic products than NfnB, forming more of the desired 4-hydroxylamine derivative of CB1954.
细菌硝基还原酶NfnB因其在与硝基还原酶前药CB1954联合用于定向酶前药疗法中的应用而成为大量研究的焦点，这种酶和前药的组合甚至进入了临床试验阶段。尽管取得了一些有前景的结果，但该研究仍存在重大局限性，例如该酶报道的最低Km值远远超过CB1954的最大剂量。由于这些局限性，目前正在研究新的酶在定向酶前药疗法中的潜在用途。一种已被证明有前景的酶是来自地衣芽孢杆菌的YfkO硝基还原酶。经研究发现，YfkO硝基还原酶的Km值比NfnB低得多（低于最大剂量），而且与前药反应时，它产生的酶促产物比例比NfnB更有利，形成更多所需的CB1954 4-羟胺衍生物。
