Shen, Sida; Benoy, Veronick; Bergman, Joel A.; Kalin, Jay H.; Frojuello, Mariana; Vistoli, Giulio; Haeck, Wanda; Van Den Bosch, Ludo; Kozikowski, Alan P. published the artcile< Bicyclic-Capped Histone Deacetylase 6 Inhibitors with Improved Activity in a Model of Axonal Charcot-Marie-Tooth Disease>, Product Details of C9H8BrFO2, the main research area is histone deacetylase inhibitor neuroprotectant; Charcot−Marie−Tooth disease; Selective histone deacetylase 6 inhibitor; hydroxamic acid; mitochondrial axonal transport; mutant HSPB1-expressing DRG neurons; tubulin acetylation.
Charcot-Marie-Tooth (CMT) disease is a disorder of the peripheral nervous system where progressive degeneration of motor and sensory nerves leads to motor problems and sensory loss and for which no pharmacol. treatment is available. Recently, it has been shown in a model for the axonal form of CMT that histone deacetylase 6 (HDAC6) can serve as a target for the development of a pharmacol. therapy. Therefore, the authors aimed at developing new selective and activity-specific HDAC6 inhibitors with improved biochem. properties. By utilizing a bicyclic cap as the structural scaffold from which to build upon, the authors developed several analogs that showed improved potency compared to tubastatin A while maintaining excellent selectivity compared to HDAC1. Further screening in N2a cells examining both the acetylation of α-tubulin and histones narrowed down the library of compounds to three potent and selective HDAC6 inhibitors. In mutant HSPB1-expressing DRG neurons, serving as an in vitro model for CMT2, these inhibitors were able to restore the mitochondrial axonal transport deficits. Combining structure-based development of HDAC6 inhibitors, screening in N2a cells and in a neuronal model for CMT2F, and preliminary ADMET and pharmacokinetic profiles, resulted in the selection of compound I that possesses improved biochem., functional, and druglike properties compared to tubastatin A.
ACS Chemical Neuroscience published new progress about Charcot-Marie-Tooth disease. 128577-47-9 belongs to class bromides-buliding-blocks, and the molecular formula is C9H8BrFO2, Product Details of C9H8BrFO2.
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary