Recent development of selective inhibitors targeting the HDAC6 as anti-cancer drugs: Structure, function and design

• Published in: Bioorganic chemistry Vol. 138; p. 106622
• Main Authors: Peng, Jie, Xie, Fei, Qin, Pengxia, Liu, Yujing, Niu, Haoqian, Sun, Jie, Xue, Haoyu, Zhao, Qianlong, Liu, Jingqian, Wu, Jingde
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2023
• Subjects: Anti-cancer; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; HDAC6; Histone Deacetylase 6 - metabolism; Histone Deacetylase Inhibitors - chemistry; Histone Deacetylases - metabolism; Humans; Neoplasms - drug therapy; Structure; Tumorigenesis; TMZ; MHC; CDK; p53; Oct4; DNMT; Arp2/3; PI3K; Next A; Akt2; UPS; Tumorigenesis; Rac1; ZnF-UBP; MTOC; MM; HSP; ErbB2; PARP1; RASSF1A; TubA; PKC; MAPK; ARID1A; YWHAZ; MSH6; K-2; ERK1/2; CAR; EB1; PD-1; MAP; SQSTM1; HDAC; MART1; Bcl-6; TYRP1; HDAC6; EGFR; CCNB1; SE14; GBM; BAG3; PD-L1; Cep70; Anti-cancer; Structure; CD; HSF-1; VEGF; STAT3; ERST; CYLD; Smad3; JAK; TIL; NES
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2023.106622

[Display omitted] •HDAC6 has emerged as a potential target for cancer treatment.•The use of benzene as linker is essential to improve HDAC6 isoform-selectivity.•This review is focused on small molecules targeting HDAC6 and their mechanism of action.•Modification of cap is the main content in the development of selective inhibitors of HDAC6.•HDAC6 inhibitors have attracted the attention of pharmaceutical chemists due to their low toxicity. HDAC6, a member of the histone deacetylase family, mainly is a cytosolic protein and regulates cell growth by acting on non-histone substrates, such as α -tubulin, cortactin, heat shock protein HSP90, programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1), that are closely related to the proliferation, invasion, immune escape and angiogenesis of cancer tissues. The approved drugs targeting the HDACs are all pan-inhibitors and have many side effects due to their lack of selectivity. Therefore, development of selective inhibitors of HDAC6 has attracted much attention in the field of cancer therapy. In this review, we will summarize the relationship between HDAC6 and cancer, and discuss the design strategies of HDAC6 inhibitors for cancer treatment in recent years.