Current development of the second generation of mTOR inhibitors as anticancer agents.

摘要: The mammalian target of rapamycin (mTOR), a serine/threonine protein kinase, acts as “master switch” for cellular anabolic and catabolic processes, regulating the rate cell growth proliferation. Dysregulation mTOR signaling pathway occurs frequently in variety human tumors, thus, has emerged an important design anticancer agents. is found two distinct multiprotein complexes within cells, mTORC1 mTORC2. These consist unique mTOR-interacting proteins are regulated by different mechanisms. Enormous advances have been made development drugs known inhibitors. Rapamycin, first defined inhibitor mTOR, showed effectiveness agent various preclinical models. Rapamycin analogues (rapalogs) with better pharmacologic properties developed. However, clinical success rapalogs limited to few types cancer. discovery that mTORC2 directly phosphorylates Akt, survival adds new insight into role This novel finding prompted efforts develop second generation inhibitors able both Here, we review recent field focus specifically on current