Novel HIF-1α inhibitor CDMP-TQZ for cancer therapy

被引：7

作者：

Chu, Po-Chen ^{[1
,2
,3
]}

Wu, Yu-Chieh ^{[4
]}

Chen, Chien-Yu ^{[4
]}

Hung, Yu-Syuan ^{[4
]}

Chang, Chih-Shiang ^{[3
,4
]}

机构：

[1] China Med Univ, Dept Cosmeceut, Taichung 40402, Taiwan

[2] China Med Univ, Grad Inst Cosmeceut, Taichung 40402, Taiwan

[3] China Med Univ, Drug Dev Ctr, Taichung 40402, Taiwan

[4] China Med Univ, Sch Pharm, Coll Pharm, Taichung 40402, Taiwan

来源：

FUTURE MEDICINAL CHEMISTRY | 2021年 / 13卷 / 12期

关键词：

anticancer agents; hypoxia-inducible factor-1; tetrahydroquinolines;

D O I：

10.4155/fmc-2020-0307

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Aim: Tumor cells adapt to hypoxic microenvironments by releasing the key transcription factor HIF-1 alpha, which promotes angiogenesis, glycolytic phenotype, metastasis and erythropoiesis, allowing proliferation amid low oxygen levels. Therefore, therapeutic targeting of HIF-1 alpha represents a viable strategy for cancer therapy. Methods & Results: The authors synthesized a series of novel tetrahydroquinazoline derivatives in six steps and demonstrated that their development had a unique ability to suppress HIF-1 alpha expression through proteasomal degradation. Conclusion: Among these compounds, CDMP-TQZ (8bf) exhibited the highest antiproliferative potency in human cancer cells, in part through downregulation of HIF-1 alpha.

引用

页码：1057 / 1072

页数：16

共 35 条

[31] Design, synthesis, and structure-activity relationships of 1-ethylpyrazole-3-carboxamide compounds as novel hypoxia-inducible factor (HIF)-1 inhibitors [J].