Therapeutic Potential of 1,3,4-Thiadiazole Scaffolds in Cancer: Targeting Receptor Tyrosine Kinases, Apoptosis, and Epigenetic Pathways

The 1,3,4-thiadiazole nucleus has emerged as a versatile scaffold in anticancer drug discovery owing to its structural flexibility, favourable pharmacological properties, and ability to modulate diverse biological targets. Recent studies demonstrate its potential in inhibiting receptor tyrosine kinases (VEGFR-2, EGFR, FLT3, and BRAF), thereby attenuating angiogenesis and tumor proliferation. In addition, several derivatives induce apoptosis through caspase activation and CDK1 inhibition, while others act as histone deacetylase inhibitors, offering opportunities for epigenetic regulation and resistance management. Activity against metabolic enzymes such as carbonic anhydrases further underscores its broad therapeutic spectrum. This review highlights advances in structure–activity relationships, target selectivity, and mechanistic insights, underscoring the therapeutic promise of 1,3,4-thiadiazole scaffolds in cancer treatment.