Targeting protein phosphatase PP2A for cancer therapy: development of allosteric pharmaceutical agents.
Targeting protein phosphatase PP2A for cancer therapy: development of allosteric pharmaceutical agents.
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DOI：
10.1042/cs20201367
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发表时间：
2021-07-16
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肿瘤起始由癌基因驱动，其激活涉及蛋白磷酸化的细胞增殖和存活的信号网络。这些途径中的蛋白激酶已被证明是药物抑制剂的有效靶点，这些药物抑制剂已发展到临床治疗各种癌症。在这里，我们提供了一个叙述的蛋白质丝氨酸/苏氨酸磷酸酶2A（PP 2A）的小分子调节剂的发展，以减少细胞增殖和生存途径的激活。这些新药促进选择的PP 2A异源三聚体形式的组装，其作用是限制细胞增殖。我们讨论了这种方法在癌症和其他人类疾病的临床中的近期翻译潜力。
Tumor initiation is driven by oncogenes that activate signaling networks for cell proliferation and survival involving protein phosphorylation. Protein kinases in these pathways have proven to be effective targets for pharmaceutical inhibitors that have progressed to the clinic to treat various cancers. Here, we offer a narrative about the development of small molecule modulators of the protein Ser/Thr phosphatase 2A (PP2A) to reduce the activation of cell proliferation and survival pathways. These novel drugs promote the assembly of select heterotrimeric forms of PP2A that act to limit cell proliferation. We discuss the potential for the near-term translation of this approach to the clinic for cancer and other human diseases.