2022年12月16日 · GLS is a mitochondrial enzyme that releases glutamine’s amide group as ammonia. CB-839 is a potent and well-tolerated GLS inhibitor with efficacy in some patients with heavily pretreated RCC (21, 22), although recent combination studies failed to achieve primary clinical end points .

2021年11月3日 · We found that RCC cells are highly dependent on glutamine for proliferation, and this dependence strongly correlated with sensitivity to telaglenstat (CB-839), an investigational, first-in-class, selective, orally bioavailable GLS inhibitor. Metabolic profiling of RCC cell lines treated with telaglenastat revealed a decrease in glutamine ...

2019年6月19日 · GLS is often upregulated in glutamine addicted cancers, enhancing glutamine metabolism for the production of energy and the biosynthesis of various cellular building blocks. CB-839 is currently in clinical trials for several tumors, including clear cell (cc)RCC, both as monotherapy and in combination with the approved therapeutic agents ...

2021年11月3日 · We found that RCC cells are highly dependent on glutamine for proliferation, and this dependence strongly correlated with sensitivity to telaglenstat (CB-839), an investigational, first-in-class, selective, orally bioavailable GLS inhibitor. Metabolic profiling of RCC cell lines treated with telaglenastat revealed a decrease in glutamine ...

2016年5月20日 · CB-839 has broad activity in preclinical models, including RCC where GLS is highly expressed. In RCC cell lines, CB-839 combines synergistically with E in vitro and in vivo, strongly inhibiting cell growth as well as glucose and glutamine metabolism.

2018年2月26日 · Background: CB-839 is a first-in-class inhibitor of GLS that targets tumor glutamine utilization, a pathway upregulated in kidney cancer. CB-839 combines with E or Cabo in pre-clinical RCC models to inhibit metabolic pathways resulting in enhanced anti-tumor activity.

2019年10月1日 · Altered glucose and glutamine (gln) metabolism is a hallmark of RCC. Glutaminase (GLS) is a key enzyme in gln metabolism and drives proliferation of RCC cells when overexpressed. Tela, a novel, first-in-clinic, selective GLS inhibitor, blocks critical gln-dependent pathways and synergizes preclinically with signal transduction inhibitors (eg, E).

谷氨酰胺酶 (GLS) 是 gln 代谢中的关键酶，当过度表达时会促进 RCC 细胞的增殖。Tela 是一种新型、临床首创的选择性 GLS 抑制剂，可阻断关键的 gln 依赖性途径，并在临床前与信号转导抑制剂（例如，E）协同作用。

2021年8月1日 · Genetic and microenvironmental factors can ‘lock’ tumor cells into a state of glutamine addiction and dependence on glutaminase (GLS). Oxidative stress and activation of the NRF2-antioxidant response pathway are conserved …

CB-839 是一种谷氨酰胺酶 (GLS) 小分子抑制剂，单独和与依维莫司 (E) 联合治疗肾细胞癌 (RCC) 患者 (pts) 的 1 期研究。 Journal of Clinical Oncology ( IF 45.3 ) Pub Date : 2016-05-20 , DOI: 10.1200/jco.2016.34.15_suppl.4568