Novel matrix metalloproteinase inhibitors: an updated patent review (2014 - 2020)

Introduction: Matrix MetalloProteinases (MMPs) are key enzymes in several pathophysiological processes connected to the extracellular matrix (ECM) degradation. Earlier clinical trials evaluating broad spectrum MMP inhibitors as cancer therapeutics failed to succeed, resulting in toxic side effects, such as musculoskeletal pain and inflammation, due to poor selectivity. As it is now recognized that some MMPs are essential for tumor progression and metastasis, but others play host-protective functions, selective MMP inhibitors are needed, and their interest has grown also for therapeutic applications beyond cancer, such as infectious, inflammatory and neurological diseases. Areas covered: This updated review describes patents concerning MMP inhibitors published within January 2014 and June 2020, with therapeutic applications spanning from cancer to inflammatory and neurological disorders. Expert opinion: Although the number of patents has decreased with respect to the previous decade, new applications provide selective matrix metalloproteinase inhibitors for therapeutic treatments beyond cancer. For several applications, the need of selective inhibitors resulted in the development of new non-hydroxamate compounds, paving the way towards a renewed interest towards MMPs as therapeutic targets. In particular, inhibitors able to cross the blood-brain barrier have been disclosed and proposed for the treatment of neurological conditions, infections, wound healing and cancer.