HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Objective To study the effects of ethanol extract of rhizoma phragmitis on liver glycogen content and glycogen synthetase (GS) in streptozotocin (STZ) induced diabetic mice. Methods The diabetic model mice were divided in-to model control group, high-dose group and low-dose group, 10 mice for each group. Another 10 normal mice were used as control group. The liver glycogen content was detected by histochemical staining of glycogen (PAS) method. The expression of GS mRNA was detected by reverse transcription polymerase chain reaction (RT-PCR) and Western blot assays. Results After PAS staining the hepatic glycogen content decreased significantly in model control group, and which was significantly increased in low-dose group and high-dose group compared with that of model control group (P＜0.01). The hepatic glyco-gen content was the highest in high-dose group compared with that of other three groups. The levels of GS mRNA and GS protein were significantly lower in model control group than those of other three groups, which were significantly lower in low-dose group than those of high-dose group (P＜0.05). Conclusion There is a dose-dependent effect of ethanol extract of rhizoma phragmitis on liver glycogen in STZ induced diabetic mice, which may be related with the increased expression of liver glycogen synthetase.