Novel Matrix Metalloproteinase-9 (MMP-9) Inhibitors in Cancer Treatment

Abstract

Matrix metalloproteinases (MMPs) belong to a family of zinc-dependent proteolytic metalloenzymes. MMP-9, a member of the gelatinase B family, is characterized as one of the most intricate MMPs. The crucial involvement of MMP-9 in extracellular matrix (ECM) remodeling underscores its significant correlation with each stage of cancer pathogenesis and progression. The design and synthesis of MMP-9 inhibitors is a potentially attractive research area. Unfortunately, to date, there is no effective MMP-9 inhibitor that passes the clinical trials and is approved by the FDA. This review primarily focuses on exploring the diverse strategies employed in the design and advancement of MMP-9 inhibitors, along with their anticancer effects and selectivity. To illuminate the essential structural characteristics necessary for the future design of novel MMP-9 inhibitors, the current narrative review highlights several recently discovered MMP-9 inhibitors exhibiting notable selectivity and potency.

Differential Expression of SRY-Related HMG-Box Transcription Factor 2, Oligodendrocyte Lineage Transcription Factor 2, and Zinc Finger E-Box Binding Homeobox 1 in Serum-Derived Extracellular Vesicles: Implications for Mithramycin Sensitivity and Targeted Therapy in High-Grade Glioma

“…Unfortunately, as of now, none of the MMP-9 inhibitors have received FDA approval. 42 The selective antitumor efficacy of Mit-A observed in our study may be attributed to the cellular heterogeneity inherent in brain tumors. This heterogeneity is potentially rooted in the presence of GSCs, which are capable of initiating distinct tumor cell lineages post tumor initiation.…”

“…To assess the potential therapeutic efficacy of inhibiting MMP-9 function in Mit-A responders, it is imperative to develop specific MMP-9 inhibitors that selectively target the tumor-promoting function while preserving its antitumor effects. Unfortunately, as of now, none of the MMP-9 inhibitors have received FDA approval …”

Synthesis of Some New 1,3,4-Oxadiazole Derivatives and Evaluation of Their Anticancer Activity

“…50 4.1.3. General Procedure for the Synthesis of the N-[2-((5-Mercapto-1,3,4-oxadiazol-2-yl)methoxy)phenyl]acetamide (3). For 6 h, a mixture of N-(2-(2-hydrazinyl-2-oxoethoxy)phenyl)acetamide (2) (0.017 mol, 3.87 g), carbon disulfide (0.025 mol, 1.90 g), and potassium hydroxide (0.025 mol, 1.40 g) in ethanol (50 mL) was refluxed.…”

“…Several studies have indicated that MMPIs (matrix metalloproteinase inhibitors) have the potential to impede cell proliferation by promoting apoptosis. 3 Heterocyclic compounds constitute 70% of the anticancer medications approved by the FDA between 2010 and 2020. 4 Heterocyclic rings exhibit their biological activity in different pathways owing to their ability to engage in various intermolecular interactions such as hydrogen bond donor/ acceptor characteristics, metal coordination complexes, Πstacking interactions, and van der Waals and hydrophobic forces.…”

“…Developed anticancer drugs target enzymes, genes, or signals that function in key steps such as angiogenesis, apoptosis, tumor invasion, and metastasis. , MMP-9, matrix metalloproteinase-9, is an enzyme responsible for supporting the cell and tissue structure. Several studies have indicated that MMPIs (matrix metalloproteinase inhibitors) have the potential to impede cell proliferation by promoting apoptosis …”