Repurposing marimastat as a broad-spectrum small-molecule inhibitor for snakebite envenoming: From oncology trials to the development of field-ready interventions.

Marimastat is a pan-catalytic MMP inhibitor that is emerging as an alternative therapy for venom bite lesions because it can antagonise metalloproteinases in snake venom, without being constrained by the production or storage requirements of antivenoms or intravenous administration. Metalloproteinases are important effector enzymes in many aspects of tissue damage caused by snake bites, so inhibition of their action should interfere with both systemic haemorrhage and local necrosis. Preclinical studies and proteomics studies have shown its effectiveness in many species of snakes and might be particularly attractive given that venom therapy requires only a short duration of treatment (3-5 days), unlike other uses of MMP inhibitors that can produce musculoskeletal toxicity. Marimastat, alone or in combination with sPLA2 inhibitors, is the basis of ongoing tests in phase II clinical trials. This drug holds the potential to complement future therapies for bringing patients to the hospital, where more treatment can be given.