Mechanistic target of rapamycin (mTOR) is a highly conserved protein kinase acting as a central regulator of cell functions. The kinase forms two distinct mTOR complexes termed as mTORC1 and mTORC2. Dysregulation of mTOR activity is associated with various pathological conditions. Inhibition of overactivated mTOR represent a rational approach in the treatment of numerous human diseases. Rapamycin is a potent natural inhibitor of mTOR exhibiting significant antitumor and immunosuppressive activity. Derivatization of rapamycin provided rapalogs, the first generation of mTOR inhibitors that selectively inhibit mTORC1 activity. Further interest of research community resulted in creation of the second generation of mTOR inhibitors involving both, mTOR kinase inhibitors and dual phosphoinositide 3-kinase (PI3K)/mTOR inhibitors. Recently, combining advances of first and second generation of mTOR inhibitors yielded in the third generation of inhibitors termed as rapalinks. Nowadays, novel inhibitors belonging to all of the three generations are still under development. These inhibitors help us better to understand role of mTOR in mTOR signaling pathway as well as in diverse human diseases. In this review, we summarize recent reported mTOR inhibitors or methods of use thereof in the treatment of various diseases.

雷帕霉素的机械靶点 (mTOR) 是一种高度保守的蛋白激酶，充当细胞功能的中心调节剂。该激酶形成两个不同的 mTOR 复合物，称为 mTORC1 和 mTORC2。mTOR 活性的失调与各种病理状况有关。抑制过度激活的 mTOR 代表了治疗多种人类疾病的合理方法。Rapamycin 是一种有效的 mTOR 天然抑制剂，具有显着的抗肿瘤和免疫抑制活性。雷帕霉素的衍生提供了 rapalogs，这是第一代选择性抑制 mTORC1 活性的 mTOR 抑制剂。研究界的进一步兴趣导致产生了第二代 mTOR 抑制剂，包括 mTOR 激酶抑制剂和双磷酸肌醇 3-激酶 (PI3K)/mTOR 抑制剂。最近，结合第一代和第二代 mTOR 抑制剂的进步，在第三代抑制剂中产生，称为 rapalinks。如今，属于所有三代的新型抑制剂仍在开发中。这些抑制剂有助于我们更好地了解 mTOR 在 mTOR 信号通路以及多种人类疾病中的作用。在这篇综述中，我们总结了最近报道的 mTOR 抑制剂或其在治疗各种疾病中的使用方法。