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**AMG 193 + sotorasib** is an investigational combination therapy comprised of two small molecule drugs: **AMG 193**, a novel orally bioavailable MTA-cooperative PRMT5 inhibitor, and **sotorasib (AMG-510, Lumakras)**, a first-in-class covalent KRAS G12C inhibitor. AMG 193 selectively targets PRMT5 in MTAP-deleted tumor cells, causing DNA damage, cell cycle arrest, and apoptosis via inhibition of symmetric dimethylarginine (SDMA) formation. Sotorasib irreversibly inhibits the mutant KRAS G12C protein, preventing oncogenic signaling. This combination has shown synergistic antitumor effects in preclinical models and is being evaluated in clinical trials for advanced solid tumors, particularly those with MTAP-deletion and KRAS G12C mutations[1][2][9]. Both drugs are developed by Amgen.
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