An updated patent review of histone Deacetylase 6 inhibitors in neurodegenerative diseases (2020-2025)

INTRODUCTION: Histone deacetylase 6 (HDAC6) inhibitors have been widely explored as potential therapeutic approaches for oncological, autoimmune, cardiovascular, and neurodegenerative disorders. Recent clinical advancement of non-hydroxamate based HDAC6 inhibitors highlights favorable drug-like properties and improved safety margins, enhancing suitability for long-term treatment. AREA COVERED: models of neurodegenerative diseases. EXPERT OPINION: Expanding interest in the development of 2-(difluoromethyl)-1,3,4-oxadiazole (1,3,4-DFMO) derivatives has yielded a diverse set of HDAC6 inhibitors with superior HDAC6 potency and selectivity and enhanced oral pharmacokinetic profiles. These characteristics have facilitated the identification of optimized drug candidates for treating both peripheral and central nervous neurodegenerative diseases. Among the emerging therapeutic applications, Charcot-Marie-Tooth (CMT) disease has become the leading focus in preclinical and early clinical development using HDAC6 inhibitors.