Synthesis and structure-activity optimization of azepane-containing derivatives as PTPN2/PTPN1 inhibitors,European Journal of Medicinal Chemistry

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Synthesis and structure-activity optimization of azepane-containing derivatives as PTPN2/PTPN1 inhibitors
European Journal of Medicinal Chemistry ( IF 6.0 ) Pub Date : 2024-04-05 , DOI: 10.1016/j.ejmech.2024.116390
Jiamin Zheng ₁ , Zhisen Zhang ₁ , Xiaoyu Ding ₁ , Deheng Sun ₁ , Lihua Min ₁ , Feng Wang ₁ , Sujing Shi ₁ , Xin Cai ₁ , Man Zhang ₁ , Alex Aliper ₂ , Feng Ren ₁ , Xiao Ding ₁ , Alex Zhavoronkov ₃

Affiliation

Protein tyrosine phosphatases PTPN2 and PTPN1 (also known as PTP1B) have been implicated in a number of intracellular signaling pathways of immune cells. The inhibition of PTPN2 and PTPN1 has emerged as an attractive approach to sensitize T cell anti-tumor immunity. Two small molecule inhibitors have been entered the clinic. Here we report the design and development of compound , a novel small molecule PTPN2/N1 inhibitor demonstrating nanomolar inhibitory potency, good oral bioavailability, and robust antitumor efficacy.

中文翻译：

PTPN2/PTPN1抑制剂含氮杂环庚烷衍生物的合成及构效优化

蛋白酪氨酸磷酸酶 PTPN2 和 PTPN1（也称为 PTP1B）与免疫细胞的许多细胞内信号传导通路有关。 PTPN2 和 PTPN1 的抑制已成为增强 T 细胞抗肿瘤免疫敏感性的一种有吸引力的方法。两种小分子抑制剂已进入临床。在这里，我们报告了化合物的设计和开发，这是一种新型小分子 PTPN2/N1 抑制剂，具有纳摩尔级抑制效力、良好的口服生物利用度和强大的抗肿瘤功效。

更新日期：2024-04-05

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