Strategies for Targeting Serine/Threonine Protein Phosphatases with Small Molecules in Cancer,Journal of Medicinal Chemistry

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Strategies for Targeting Serine/Threonine Protein Phosphatases with Small Molecules in Cancer
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2021-06-22 , DOI: 10.1021/acs.jmedchem.1c00631
Qiuyue Zhang _{1,

2} , Zhongjiao Fan _{1,

2} , Lianshan Zhang ₃ , Qidong You _{1,

2} , Lei Wang _{1,

2}

Affiliation

Among numerous posttranslational regulation patterns, phosphorylation is reversibly controlled by the balance of kinases and phosphatases. The major form of cellular signaling involves the reversible phosphorylation of proteins on tyrosine, serine, or threonine residues. However, altered phosphorylation levels are found in diverse diseases, including cancer, making kinases and phosphatases ideal drug targets. In contrast to the success of prosperous kinase inhibitors, design of small molecules targeting phosphatase is struggling due to past bias and difficulty. This is especially true for serine/threonine phosphatases, one of the largest phosphatase families. From this perspective, we aim to provide insights into serine/threonine phosphatases and the small molecules targeting these proteins for drug development, especially in cancer. Through highlighting the modulation strategies, we aim to provide basic principles for the design of small molecules and future perspectives for the application of drugs targeting serine/threonine phosphatases.

中文翻译：

在癌症中靶向小分子丝氨酸/苏氨酸蛋白磷酸酶的策略

在众多翻译后调控模式中，磷酸化受激酶和磷酸酶平衡的可逆控制。细胞信号传导的主要形式涉及蛋白质在酪氨酸、丝氨酸或苏氨酸残基上的可逆磷酸化。然而，在包括癌症在内的多种疾病中都发现了磷酸化水平的改变，这使得激酶和磷酸酶成为理想的药物靶点。与繁荣的激酶抑制剂的成功相反，由于过去的偏见和困难，靶向磷酸酶的小分子的设计正在努力。对于最大的磷酸酶家族之一的丝氨酸/苏氨酸磷酸酶尤其如此。从这个角度来看，我们的目标是深入了解丝氨酸/苏氨酸磷酸酶和靶向这些蛋白质的小分子，用于药物开发，尤其是在癌症中。

更新日期：2021-07-08

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