Huashen Xu, Jie Zhang, Junning Zhuang, Yuanguang Chen, Lu Chen, Jianmin Wang, Ruolin Cao, Fuqin Liu, Kaibo Wang, Xiaoyu Zhang, Lihui Wang, Guoliang Chen
We formerly reported that EZH2 inhibitors sensitized HIF-1 inhibitor-resistant cells and inhibited HIF-1α to promote SUZ12 transcription, leading to enhanced EZH2 enzyme activity and elevated H3K27me3 levels, and conversely, inhibition of EZH2 promoted HIF-1α transcription. HIF-1α and EZH2 interacted to form a negative feedback loop that reinforced each other's activity. In this paper, a series of 2,2- dimethylbenzopyran derivatives containing pyridone structural fragments were designed and synthesized with DYB-03, a HIF-1α inhibitor previously reported by our group, and Tazemetostat, an EZH2 inhibitor approved by FDA, as lead compounds...
April 30, 2024: Bioorganic Chemistry