MMP inhibitor(Paratek Pharmaceuticals)

Matrix metalloproteinases (MMPs) are involved in the degradation of the extracellular matrix (ECM) and are found to participate in all stages of tumour progression including modifying signalling pathways, regulating cytokines and promoting tumour growth, particularly by inducing angiogenesis and facilitating cancer spread. Extensive research has been concentrated on identifying and developing MMP inhibitors for cancer treatment, including melanoma, with particular focus on MMP‐2, MMP‐9 and MMP‐14. MMP‐2 and MMP‐9 are gelatinases involved in collagen degradation, tumour invasion and angiogenesis, while MMP‐14 activates other MMPs and promotes tumour cell migration. Early broad‐spectrum MMP inhibitors showed limited success and significant side effects. However, selective MMP inhibitors offer a more targeted approach that may address these problems. By focusing on specific MMPs essential for melanoma invasion, metastasis and angiogenesis, these inhibitors have the potential to improve treatment efficacy and reduce the off‐target effects seen with earlier broad‐spectrum therapies. Recent years have seen a marked increase in studies on natural MMP inhibitors for melanoma, driven by their biocompatibility and reduced side effects. In addition to inhibiting MMPs, many of these inhibitors also provide antioxidant, anti‐inflammatory and immune‐modulatory benefits, thus enhancing their therapeutic potential and overall effectiveness in cancer treatment. These findings highlight the promising role of MMP inhibitors in melanoma therapy, suggesting a shift towards more targeted and combinatory treatment strategies. This review aims to provide an up‐to‐date overview of the advancements and therapeutic prospects of both synthetic and natural MMP inhibitors in melanoma treatment.

Diabetic wounds are a class of chronic wounds that exhibit significant healing abnormalities due to dysregulated cytokines, growth factors, and unique cellular expressions, currently affecting an estimated 9.1-26.1 million people per year globally. Matrix metalloproteinases (MMPs), angiogenic factors, and inflammatory mediators remain the key determinants for managing diabetic wounds. Vascular endothelial growth factor (VEGF) is one of the most prominent types of growth factors induced during angiogenesis in general and cell proliferation pathways. Chronic hyperglycemia, neuropathy, and inflammation associated with diabetes disorders affect cellular responses, blood circulation, and immunological systems impair normal wound healing. This reduced effectiveness of current management strategies is reflected in the high number of delayed wounds among diabetic patients due to escalated oxidative stress and impaired signaling pathways, which prevent healing, calling for new therapies. MMPs are essential for tissue remodeling, but excess levels of MMPs predispose tissues to matrix degradation and interruption in cell signaling leading thereby prolonging inflammation seen in diabetic wounds. Efficient wound healing requires a balanced relationship regarding matrix metalloproteinases and tissue inhibitors of metalloproteinases (TIMPs). New regenerative solutions, such as stem cells, platelet-rich plasma (PRP), gene therapies, and MMP inhibitors that can re-establish angiogenesis; decrease inflammation; and stimulate growth factor signaling, suggest promising strategies for improved diabetic wound healing. Hyperbaric oxygen therapy allows tissue regeneration and reduces the area of ulceration, bringing other benefits. In the future, therapeutics should focus on multifunctional and responsive strategies that include anti-inflammatory agents, cytokine modulators, and stem cell treatments that exhibit superior efficacy in comparison to conventional therapies when assessed clinically. Novel advanced combination strategies represent a realistic route to targeted therapies that meet clinical needs and have the potential capability for utilizing mechanistic insights, both creative in their implementation of recently developed techniques as well as applied on a broader scale through the evidence-based management across diabetic wounds offering better outcomes and quality of life amongst increasing diabetic commonalities.