TYMS and neoplasm: In another study, a series of (E)-N-(2-benzylhydrazine-1-carbonyl)phenyl-2,4-deoxy-1,2,3,4-tetrahydropyrimidine-5-sulfonamide derivatives was developed to optimize both TS inhibition and antiproliferative activity.115 The hit compound 12 (IC50 = 17.21 nM) exhibited superior efficacy to pemetrexed (PTX) in vitro and in vivo, effectively suppressing tumor growth and angiogenesis in NSCLC models.