1.Discovery of a potential hematologic malignancies therapy: Selective and potent HDAC7 PROTAC degrader targeting non-enzymatic function.
Yuheng JIN ; Xuxin QI ; Xiaoli YU ; Xirui CHENG ; Boya CHEN ; Mingfei WU ; Jingyu ZHANG ; Hao YIN ; Yang LU ; Yihui ZHOU ; Ao PANG ; Yushen LIN ; Li JIANG ; Qiuqiu SHI ; Shuangshuang GENG ; Yubo ZHOU ; Xiaojun YAO ; Linjie LI ; Haiting DUAN ; Jinxin CHE ; Ji CAO ; Qiaojun HE ; Xiaowu DONG
Acta Pharmaceutica Sinica B 2025;15(3):1659-1679
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.
2.The clinical value of the special functions of DSA in interventional embolization for uterine fibroids
Journal of Interventional Radiology 2009;18(11):868-871
Objective To evaluate the special functions of DSA in interventional embolization therapy for uterine fibroids. Methods The special functions of DSA, including 3D-DSA, the optimal working position and road-mapping technique, were utilized in performing interventional embolization therapy for uterine fibroids in twenty-six cases (experimental group). Routine DSA angiography was employed in twenty cases (control group). The volume of contrast media used, the time of completing the interventional procedure and the total fluoroscopic time in two groups were compared and the results were analyzed. Results The difference in the volume of contrast agent used and in the total fluoroscopic time between two groups was statistically significant (P < 0.05), although no significant difference in the time of completing interventional procedure existed between two groups (P > 0.05). Conclusion In treating uterine fibroids with interventional embolization, the use of the special functions of DSA can reduce the manipulation time and lower the operation risk. Moreover, the technique of visible 3D reconstruction image is of great significance in guiding the procedure.
3.Distribution of apolipoprotein E genotype in NIDDM patients with vascular complications
Guangda XIANG ; Bangshun XIA ; Yushen HE
Chinese Medical Journal 1998;(6):506-506
Objective To investigate the distribution of apolipoprotein E (ApoE) genotype among different vascular complications and the variation of allele frequency with age in non-insulin-dependent diabetes mellitus (NIDDM).Methods 125 NIDDM patients and 50 healthy individuals were selected randomly. Polymerase chain reaction was used to determine their ApoE genotypes.Results The prevalence of ∈3/3 in any vascular complication group was 59.3%, which was significantly lower than 76.0% in controls (P<0.05). The prevalences of ∈3/3, ∈4/3 and ∈4 in coronary heart disease (CHD) group were 51.8%, 33.9% and 20.5%, respectively, which were significantly lower (∈3/3, P<0.01) or higher (∈4/3, P<0.01; ∈4, P<0.05) than those in the controls, respectively. The ∈4 frequency was significantly lower in the elderly than in the non-elderly group of NIDDM (P<0.05).Conclusion ∈4 increases the risk for vascular complications, especially CHD, and ∈4 may affect the life expectancy of NIDDM patients.

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