Current Status of the Use of Multifunctional Enzymes as Anti-Cancer Drug Targets

Abstract

Fighting cancer is one of the major challenges of the 21st century. Among recently proposed treatments, molecular-targeted therapies are attracting particular attention. The potential targets of such therapies include a group of enzymes that possess the capability to catalyze at least two different reactions, so-called multifunctional enzymes. The features of such enzymes can be used to good advantage in the development of potent selective inhibitors. This review discusses the potential of multifunctional enzymes as anti-cancer drug targets along with the current status of research into four enzymes which by their inhibition have already demonstrated promising anti-cancer effects in vivo, in vitro, or both. These are PFK-2/FBPase-2 (involved in glucose homeostasis), ATIC (involved in purine biosynthesis), LTA4H (involved in the inflammation process) and Jmjd6 (involved in histone and non-histone posttranslational modifications). Currently, only LTA4H and PFK-2/FBPase-2 have inhibitors in active clinical development. However, there are several studies proposing potential inhibitors targeting these four enzymes that, when used alone or in association with other drugs, may provide new alternatives for preventing cancer cell growth and proliferation and increasing the life expectancy of patients.

Regulative Roles of Metabolic Plasticity Caused by Mitochondrial Oxidative Phosphorylation and Glycolysis on the Initiation and Progression of Tumorigenesis

“…In contrast to HK, which is the most important rate-limiting enzyme of glycolysis, targeted drugs acting solely on PFK may have the same anti-cancer effect [ 156 ]. For instance, mitochondrial VDAC can bind not only with HK-2 but also with PFK [ 157 , 158 ].…”

Metabolomics Combined with Network Pharmacology-Based Strategy to Reveal the Underlying Mechanism of Zhenhuang Submicron Emulsion in Treating Oropharyngeal Mucositis Complications of Radiation Therapy for Head and Neck Cancer

“…The catalytic activity of leukotriene A4 hydrolase (LTA4H) plays an important role in inflammatory processes; it has two distinct but overlapping active sites that confer different catalytic activities. 35 LTB4 is involved in inducing anti-microbial factors, the release of inflammatory mediators, enhancing phagocytosis, and is also implicated in diseases in which neutrophils are strongly involved. 36 In allergic mucosal inflammation, LTB4 expression levels are significantly increased in Neutrophils, monocytes, and lymphocytes, suggesting a strong involvement in this process.…”

Chalcone Derivatives with a High Potential as Multifunctional Antioxidant Neuroprotectors

“…Moreover, such a nature imposes difficult challenges for developing efficient treatments. Thus, a new paradigm in the drug design has emerged: Finding single chemical entities with multiple biological activities. − …”