König Beate, Hansen Finn K
Department of Pharmaceutical and Cell Biological Chemistry, Pharmaceutical Institute, University of Bonn, An der Immenburg 4, 53121 Bonn, Germany.
ACS Pharmacol Transl Sci. 2024 Feb 20;7(3):899-903. doi: 10.1021/acsptsci.4c00031. eCollection 2024 Mar 8.
Histone deacetylase 6 (HDAC6) is an important target for the treatment of oncological and non-oncological diseases. Established HDAC6 inhibitors feature a hydroxamic acid as a zinc-binding group (ZBG) and thus possess mutagenic and genotoxic potential. Recently, the 2-(difluoromethyl)-1,3,4-oxadiazole (DFMO) group emerged as a novel ZBG. In this Viewpoint, we summarize the discovery of the mode of action of DFMOs. Additionally, we discuss opportunities and challenges in the journey toward the clinical development of DFMO-based drugs for the treatment of HDAC6-driven diseases.
组蛋白去乙酰化酶6(HDAC6)是治疗肿瘤和非肿瘤疾病的重要靶点。已有的HDAC6抑制剂以异羟肟酸作为锌结合基团(ZBG),因此具有诱变和基因毒性潜力。最近,2-(二氟甲基)-1,3,4-恶二唑(DFMO)基团成为一种新型的锌结合基团。在这一观点中,我们总结了DFMO作用模式的发现。此外,我们还讨论了基于DFMO的药物用于治疗HDAC6驱动疾病的临床开发过程中的机遇和挑战。