Advances in the Therapeutic Targeting of Human Matrix Metalloproteinases in Health and Disease

Matrix metalloproteinases (MMPs) are multi-domain proteins that degrade and remove the ECM molecules from the tissue. Under physiologic conditions, the MMPs activity is regulated by the activation of inhibitory precursor zymogens and tissue inhibitors of metalloproteinases (TIMPs). Besides, the activities of MMPs are significantly low in the normal steady-state tissues, and expression is transcriptionally modulated by several inflammatory cytokines, growth factors, and hormones. However, MMPs have been shown to be dysregulated in pathological conditions resulting in several diseases and disorders. Thus, MMPs have been in the spotlight of the pharmaceutical drug discovery industry as a potential drug target for more than half a century, and the search for useful inhibitors is already ongoing. Several synthetic inhibitors have been trialed unsuccessfully due to a lack of inhibitor specificity and insufficient knowledge of the complex pathology. Recent advancements in computational simulations, structural methods, and biochemistry have revealed a plethora of insights into the structure and function of MMPs and thus our newly acquired knowledge can be translated into a strategy for the development of potential therapeutics against MMP related disorders.

This Research Topic aims to collect articles that highlight the promising strategies driven from small molecules, engineered proteins, clinical antibodies, and more. Recently, advanced therapeutic synthetic drug molecules, including bioactive aptamers, peptides, and drug-conjugates have found extensive applications in the fields of drug discovery using both computational and in vitro approaches. The perspective of using such therapeutic agents is to find the non-toxic, selective, and specific inhibitors for either a single member or group of MMPs simultaneously. Additionally, the development of advanced therapeutics against MMPs with a significantly sharper selectivity profile outperformed the early inhibitors in terms of reduced side effects. These advanced therapeutics offer several advantages over traditional inhibitors, including specific and selective modulation of MMPs, Thus, the development and evaluation of potential therapeutics with unique physical and biochemical characteristics targeting MMPs directly or indirectly by modulation of the MMP network under pathological conditions are of great importance, with applications to conditions such as Alzheimer’s disease, arthritis, asthma, cancer, cardiovascular diseases, chronic ulcers, encephalomyelitis, multiple sclerosis, nephritis, and tumor metastasis. This Research Topic is intended to become an international platform for researchers to summarize the most recent developments and ideas in the field of human MMPs, with special emphasis on synthetic drug molecules, bioactive, aptamers, peptides, and drug-conjugates, and their roles as therapeutics.  

We welcome Original Research, Review, Mini Review, and Perspectives on the advancement of human matrix metalloproteinases and their inhibitors for diseases and disorders. Areas of interest could include, but are not limited to:

• Synthesis and characterization of potential small molecules and other therapeutics for the human MMPs.

• Pharmaceutical approaches to interfere with the MMP network.

• Studies on the modulation of MMPs expression in diseases

• Studies on current therapeutics with potential for inhibition or modulation of MMPs