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.

AIM: To explore the molecular mechanism of brain tissue injury induced by lipopolysaccharide(LPS),the effects of panaxadiol(PDS) on the expression of nuclear factor kappa B(NF-?B) in cerebral cortex of rat with LPS shock were studied.METHODS: Rats were randomly divided into LPS group,LPS+dexamethasone group,LPS+PDS group and control group.The DNA binding activity and protein expression of NF-?B were observed.These indices were assayed at 1 h and 4 h after intravenous injection of LPS(4 mg?kg-1).RESULTS: EMSA showed that PDS inhibited NF-?B DNA-binding activity in nuclear extracts at both 1 h and 4 h after LPS injection,compared with the LPS group(P