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Cancer refers to the group of diseases characterized by uncontrolled growth of abnormal cells. It spreads throughout the body which makes this disease one of the huge global threats to mankind. Intensive research over the years has established deregulation of mam-malian target of rapamycin pathway in cancer. This has led to the development of mammalian target of rapamycin inhibitors. Several inhibitors of the mammalian target of rapamycin are under preclinical and early clinical trials. Researchers have investigated a series of furoquinoline, phenyl sulphonylureas, 4-acrylamido-quinoline, pyrazolochalcones, imidazole [4,5-b] pyridine, thienopyrimidine, aminopyrimidin scaffolds in the last three years. This review provides comprehensive information and critical discussions on designing of novel selective inhibitors of mammalian target of rapamycin with superior activity in the treatment of cancer.