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S-3304 is a potent, orally active, noncytotoxic small molecule inhibitor of matrix metalloproteinases (MMPs), primarily targeting MMP-2 and MMP-9. Developed by Shionogi as an anticancer agent, it was designed to inhibit extracellular matrix degradation, thereby suppressing angiogenesis, tumor growth and invasion, and metastasis. Preclinical studies demonstrated prolonged survival in mouse xenograft models. In clinical trials for advanced solid tumors and non-small cell lung cancer (NSCLC), S-3304 was well tolerated with gastrointestinal side effects being most common. The drug achieved plasma concentrations sufficient to inhibit intratumoral MMP activity but did not progress beyond early-phase clinical development[1][3][6][7].
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