acy-738 and Central-Nervous-System-Diseases

Histone deacetylase 6 inhibitors (HDAC6is) have been applied to certain cancer diseases and more recently to central nervous system (CNS) disorders including Rett syndrome, Alzheimer's and Parkinson's diseases, and major depressive disorder. Brain penetrance is the major challenge for the development of HDAC6is as potential therapeutics for CNS disorders due in part to the polarity of hydroxamate ZBG. Hence, only a handful of brain-penetrant HDAC6is have been reported and a few display appropriate in vitro and in vivo activities in models of neurological diseases in last decades. This review summarizes the contemporary research being done on HADC6is with brain penetration both the biological pathways involved and the structural modification attempts.

Topics: Animals; Biological Transport; Blood-Brain Barrier; Brain; Central Nervous System Diseases; Histone Deacetylase 6; Humans; Hydroxamic Acids; Male; Models, Molecular; Neuroprotective Agents; Protein Binding; Protein Conformation; Signal Transduction; Structure-Activity Relationship