Shen, Sida; Picci, Cristina; Ustinova, Kseniya; Benoy, Veronick; Kutil, Zsofia; Zhang, Guiping; Tavares, Mauricio T.; Pavlicek, Jiri; Zimprich, Chad A.; Robers, Matthew B.; Van Den Bosch, Ludo; Barinka, Cyril; Langley, Brett; Kozikowski, Alan P. published the artcile< Tetrahydroquinoline-Capped Histone Deacetylase 6 Inhibitor SW-101 Ameliorates Pathological Phenotypes in a Charcot-Marie-Tooth Type 2A Mouse Model>, Computed Properties of 128577-47-9, the main research area is tetrahydroquinoline phenylhydroxamate synthesis SW101 HDAC6 neurodegenerative disorder; Charcot Marie Tooth disease tetrahydroquinoline Structure activity.
Histone deacetylase 6 (HDAC6) is a promising therapeutic target for the treatment of neurodegenerative disorders. SW-100 (1a), a phenylhydroxamate-based HDAC6 inhibitor (HDAC6i) bearing a tetrahydroquinoline (THQ) capping group, is a highly potent and selective HDAC6i that was shown to be effective in mouse models of Fragile X syndrome and Charcot-Marie-Tooth disease type 2A (CMT2A). In this study, we report the discovery of a new THQ-capped HDAC6i, termed SW-101 (1s), that possesses excellent HDAC6 potency and selectivity, together with markedly improved metabolic stability and druglike properties compared to SW-100 (1a). X-ray crystallog. data reveal the mol. basis of HDAC6 inhibition by SW-101 (1s). Importantly, we demonstrate that SW-101 (1s) treatment elevates the impaired level of acetylated α-tubulin in the distal sciatic nerve, counteracts progressive motor dysfunction, and ameliorates neuropathic symptoms in a CMT2A mouse model bearing mutant MFN2. Taken together, these results bode well for the further development of SW-101 (1s) as a disease-modifying HDAC6i.
Journal of Medicinal Chemistry published new progress about Charcot-Marie-Tooth disease. 128577-47-9 belongs to class bromides-buliding-blocks, and the molecular formula is C9H8BrFO2, Computed Properties of 128577-47-9.
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary