Faculty of Pharmacy, 'Carol Davila' University of Medicine and Pharmacy, 020956 Bucharest, Romania.
Department of Biochemistry and Microbiology, Nelson Mandela University, Port Elizabeth 6031, South Africa.
Int J Oncol. 2018 Dec;53(6):2319-2331. doi: 10.3892/ijo.2018.4597. Epub 2018 Oct 16.
Protein kinase B (Akt), similar to many other protein kinases, is at the crossroads of cell death and survival, playing a pivotal role in multiple interconnected cell signaling mechanisms implicated in cell metabolism, growth and division, apoptosis suppression and angiogenesis. Akt protein kinase displays important metabolic effects, among which are glucose uptake in muscle and fat cells or the suppression of neuronal cell death. Disruptions in the Akt‑regulated pathways are associated with cancer, diabetes, cardiovascular and neurological diseases. The regulation of the Akt signaling pathway renders Akt a valuable therapeutic target. The discovery process of Akt inhibitors using various strategies has led to the identification of inhibitors with great selectivity, low side‑effects and toxicity. The usefulness of Akt emerges beyond cancer therapy and extends to other major diseases, such as diabetes, heart diseases, or neurodegeneration. This review presents key features of Akt structure and functions, and presents the progress of Akt inhibitors in regards to drug development, and their preclinical and clinical activity in regards to therapeutic efficacy and safety for patients.
蛋白激酶 B（Akt）与许多其他蛋白激酶类似，处于细胞死亡和存活的交汇点，在涉及细胞代谢、生长和分裂、凋亡抑制和血管生成的多种相互关联的细胞信号机制中发挥关键作用。Akt 蛋白激酶具有重要的代谢作用，其中包括肌肉和脂肪细胞中的葡萄糖摄取或神经元细胞死亡的抑制。Akt 调节途径的中断与癌症、糖尿病、心血管和神经疾病有关。Akt 信号通路的调节使 Akt 成为一个有价值的治疗靶点。使用各种策略发现 Akt 抑制剂的过程导致了具有高选择性、低副作用和低毒性的抑制剂的鉴定。Akt 的用途不仅限于癌症治疗，还扩展到其他主要疾病，如糖尿病、心脏病或神经退行性疾病。本文介绍了 Akt 的结构和功能的主要特征，并介绍了 Akt 抑制剂在药物开发方面的进展，以及它们在治疗效果和患者安全性方面的临床前和临床活性。
