Beyond classical scaffolds, recent efforts have produced novel TS-inhibitory chemotypes, including 2-thiopyrimidine-5-carbonitrile derivatives, which reduce TS expression and suppress tumor cell proliferation, migration, and 3D spheroid formation in preclinical studies.117,146,147 Some representatives additionally induce mitochondrial apoptosis and anti-angiogenic activity, highlighting the potential of hybrid or multifunctional designs. The gene discussed is TYMS; the disease is neoplasm.