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**Otaplimastat + alteplase** is an investigational combination therapy aimed at the treatment of **acute ischemic stroke**. Alteplase is a recombinant tissue plasminogen activator (rtPA), approved for thrombolytic therapy, that binds to fibrin in thrombi and converts plasminogen to plasmin, promoting clot dissolution. Otaplimastat (SP-8203) is a small molecule with a quinazoline-2,4-dione scaffold developed as a neuroprotectant; it functions primarily by inhibiting matrix metalloproteinases (MMPs) via upregulation of tissue inhibitor of metalloproteinase-1 (TIMP1), thereby reducing edema, hemorrhagic transformation, and neurotoxicity associated with delayed alteplase treatment. Preclinical and early clinical studies suggest that otaplimastat may extend the therapeutic window of alteplase and mitigate its adverse effects such as intracerebral hemorrhage and blood-brain barrier disruption[2][3].
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