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ST-182 is a preclinical, multifunctional small molecule kinase inhibitor developed by researchers at the University of Michigan. It is designed to simultaneously target and inhibit key nodes in both the MAPK and PI3K/AKT/mTOR signaling pathways, specifically MEK1, the alpha, beta, delta, and gamma isoforms of PI3K, and mTOR. This multi-targeting approach is intended to overcome the compensatory cross-talk and resistance mechanisms often observed with single-agent therapies. ST-182 features unique physiochemical properties, including high lipophilicity, which promote direct lymphatic system uptake (exceeding 95%) following oral administration. This lymphatic-directed absorption bypasses first-pass hepatic metabolism, potentially enhancing bioavailability and reducing systemic toxicities. Preclinical studies have demonstrated its efficacy in reducing tumor growth and metastasis in orthotopic mammary tumor models, as well as showing therapeutic potential in diffuse intrinsic pontine glioma (DIPG), experimental autoimmune encephalomyelitis (EAE), and idiopathic pulmonary fibrosis.
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