Authors
Justyna M Gawel, Andrew E Shouksmith, Yasir S Raouf, Nabanita Nawar, Krimo Toutah, Shazreh Bukhari, Pimyupa Manaswiyoungkul, Olasunkanmi O Olaoye, Johan Israelian, Tudor B Radu, Aaron D Cabral, Diana Sina, Abootaleb Sedighi, Elvin D de Araujo, Patrick T Gunning
Publication date
2020/9/1
Journal
European Journal of Medicinal Chemistry
Volume
201
Pages
112411
Publisher
Elsevier Masson
Description
Abstract Dysregulated Histone Deacetylase (HDAC) activity across multiple human pathologies have highlighted this family of epigenetic enzymes as critical druggable targets, amenable to small molecule intervention. While efficacious, current approaches using non-selective HDAC inhibitors (HDACi) have been shown to cause a range of undesirable clinical toxicities. To circumvent this, recent efforts have focused on the design of highly selective HDACi as a novel therapeutic strategy. Beyond roles in regulating transcription, the unique HDAC6 (with two catalytic domains) regulates the deacetylation of α-tubulin; promoting growth factor-controlled cell motility, cell division, and metastatic hallmarks. Recent studies have linked aberrant HDAC6 function in various hematological cancers including acute myeloid leukaemia and multiple myeloma. Herein, we report the discovery, in vitro characterization, and biological …
Total citations
202020212022202320241712136
Scholar articles
JM Gawel, AE Shouksmith, YS Raouf, N Nawar… - European Journal of Medicinal Chemistry, 2020