Recent advances in the design and development of small-molecule MMP-2 inhibitors.

MMP-2 is crucial for ECM remodeling and embryonic development. MMP-2 is a key biomolecular target for its strong association with cancer progression, metastasis, and angiogenesis. Again, the implication of MMP-2 in other diseases is well-established. Though several MMPIs failed after extensive clinical studies due to a lack of selectivity, poor pharmacokinetics, and dose-related toxicities, there is still a huge opportunity to develop specific MMP-2 inhibitors to battle against such life-threatening diseases as cardiovascular diseases, diabetes, renal diseases, and inflammatory diseases. Here, the development of small-molecule MMP-2 inhibitors for the last five years, comprising various ZBGs and diverse scaffolds, as well as their structural information along with their in-depth biological implications in cancers and other diseases, has been discussed in detail. This study may reinforce the importance of potential and selective MMP-2 inhibition as a therapeutic approach, paving the way for future research into optimizing small-molecule MMP-2 inhibitors for clinical applications. As the development of these MMP-2 inhibitors advances, further in vivo studies and structure-activity relationship optimizations will be essential to translate these promising results into viable therapeutic options for several cancers and other life-threatening diseases.