Matrix metalloproteinase-2 and Matrix metalloproteinase-3 (MMP-2 and MMP-3)

Matrix metalloproteinase-2 (MMP-2), also known as gelatinase A, and Matrix metalloproteinase-3 (MMP-3), known as stromelysin-1, are zinc-dependent endopeptidases that play pivotal roles in the degradation and remodeling of the extracellular matrix (ECM) (UniProt P08253; UniProt P08254). These enzymes are involved in normal physiological processes such as embryonic development, wound healing, and angiogenesis, but their over-expression is linked to various pathological states (Nagase et al., 2006, Cardiovascular Research). In cancer, MMP-2 and MMP-3 facilitate tumor invasion and metastasis by degrading basement membrane components like type IV collagen and laminin (Cui et al., 2017, Frontiers in Physiology). They are also significant mediators in inflammatory diseases, particularly rheumatoid arthritis, where MMP-3 contributes to cartilage destruction (Lerner et al., 2018, Journal of Internal Medicine). Pharmacological targeting of these enzymes has primarily involved small-molecule inhibitors like marimastat and batimastat, which bind to the catalytic zinc ion (DrugBank Online). However, clinical development has been hindered by a lack of selectivity and the occurrence of musculoskeletal syndrome, a painful side effect involving joint and muscle stiffness (Fields, 2019, Protein Science).

Other names

Gelatinase A72 kDa type IV collagenaseStromelysin-1Transin-1MMP2MMP3

Inhibition of the proteolytic activity by binding to the zinc-containing catalytic domain, preventing the degradation of extracellular matrix components.