Matrix metalloproteinases (MMP-2, MMP-3, MMP-9, MMP-13, MMP-14) (MMPs)

Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases responsible for the degradation and remodeling of the extracellular matrix (ECM). This specific group—comprising MMP-2, MMP-3, MMP-9, MMP-13, and MMP-14—plays critical roles in both physiological processes like wound healing and pathological conditions such as cancer metastasis and chronic inflammation [1, 2, 3]. MMP-2 and MMP-9 (gelatinases) are heavily involved in angiogenesis and tumor invasion, while MMP-3 (stromelysin) and MMP-13 (collagenase) are key drivers of cartilage destruction in arthritis [7, 8, 10]. MMP-14 (MT1-MMP) is a membrane-bound protease that acts as a master regulator by activating other MMPs, including MMP-2 [3, 11]. Despite their clear involvement in disease, therapeutic targeting has been challenging; early broad-spectrum inhibitors failed in clinical trials due to dose-limiting musculoskeletal toxicity [4, 11]. Modern drug development focuses on achieving high selectivity for specific MMP isoforms or targeting their non-catalytic domains to avoid systemic side effects [11, 13].

Other names

Matrix metalloproteinase 2 (MMP-2)Matrix metalloproteinase 3 (MMP-3)Matrix metalloproteinase 9 (MMP-9)Matrix metalloproteinase 13 (MMP-13)Matrix metalloproteinase 14 (MMP-14)Gelatinase A (MMP-2)Stromelysin-1 (MMP-3)Gelatinase B (MMP-9)Collagenase 3 (MMP-13)Membrane-type 1 matrix metalloproteinase (MT1-MMP)

Inhibition of proteolytic activity by chelating or binding to the catalytic zinc ion in the active site, thereby preventing the degradation of extracellular matrix substrates and the processing of bioactive molecules [4, 6, 11].