Overview of the Development of Glutaminase Inhibitors: Achievements and Future Directions.,Journal of Medicinal Chemistry

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Overview of the Development of Glutaminase Inhibitors: Achievements and Future Directions.
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2018-09-07 , DOI: 10.1021/acs.jmedchem.8b00961
Xi Xu ₁ , Ying Meng ₁ , Lei Li ₁ , Pengfei Xu ₁ , Jubo Wang ₁ , Zhiyu Li _{1,

2} , Jinlei Bian _{1,

2}

Affiliation

It has been demonstrated that glutamine metabolism has become the main energy and building blocks supply for the growth and viability of a potentially large subset of malignant tumors. The glutamine metabolism often depends upon mitochondrial glutaminase (GLS) activity, which converts glutamine to glutamate and serves as a significant role for bioenergetic processes. Thus, recently, the GLS has become a key target for small molecule therapeutic intervention. Numerous medicinal chemistry studies are currently aimed at the design of novel and potent inhibitors for GLS, however, to date, only one compound (named CB-839) have entered clinical trials for the treatment of advanced solid tumors and hematological malignancies. The perspective summarizes the progress in the discovery and development of GLS inhibitors, including the potential binding site, biochemical techniques for inhibitor identification, and approaches for identifying small-molecule inhibitors, as well as future therapeutic perspectives in glutamine metabolism are also put forward in order to provide reference and rational for the drug discovery of novel and potent glutamine metabolism modulators.

中文翻译：

谷氨酰胺酶抑制剂的发展概述：成就和未来方向。

已经证明，谷氨酰胺代谢已经成为潜在的大量恶性肿瘤的生长和生存力的主要能量和基石供应。谷氨酰胺的代谢通常取决于线粒体谷氨酰胺酶（GLS）的活性，该活性将谷氨酰胺转化为谷氨酸，并在生物能过程中发挥重要作用。因此，最近，GLS已成为小分子治疗干预的关键目标。目前，许多药物化学研究旨在设计新型和有效的GLS抑制剂，然而，迄今为止，只有一种化合物（命名为CB-839）已进入临床试验，用于治疗晚期实体瘤和血液系统恶性肿瘤。该观点概述了GLS抑制剂的发现和开发方面的进展，包括潜在的结合位点，

更新日期：2018-08-27

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