Abstract 1657: Discovery of a first-in-class multifunctional TYMS non-classical antifolate inhibitors with potent in vivo activity that prolongs survival
Abstract:Thymidylate synthase (TYMS/TS) is overexpressed in many cancer types and is commonly associated with advanced disease. TYMS catalyzes the de novo synthesis reaction of deoxythymidine monophosphate (dTMP), one of the building blocks of DNA. Although TYMS inhibitors have served as components of chemotherapy regimens, the currently available inhibitors induce TYMS overexpression or alter folate transport/metabolism feedback pathways that tumor cells exploit for drug resistance limiting overall benefit. Here we re… Show more
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