RTI uses cookies to offer you the best experience online. By clicking “accept” on this website, you opt in and you agree to the use of cookies. If you would like to know more about how RTI uses cookies and how to manage them please view our Privacy Policy here. You can “opt out” or change your mind by visiting: http://optout.aboutads.info/. Click “accept” to agree.
Stereospecific inhibition of ethanol potentiation on glycine receptor by M554 stereoisomers
Vásquez, P. A., San Martín, L., Argel, Y., Riquelme, C., Torres, J., Vidal, F., Cayuman, F., Castro, P., Fuentealba, J., Moraga-Cid, G., Yevenes, G., Jin, C., Jiménez, V. A., & Guzmán, L. (2020). Stereospecific inhibition of ethanol potentiation on glycine receptor by M554 stereoisomers. Journal of Chemical Information and Modeling, 60(12), 6634-6641. https://doi.org/10.1021/acs.jcim.0c00943
Blocking the interaction between the Gβγ protein and the glycine receptor (GlyR) has emerged as a promising pharmacological strategy to treat acute alcohol intoxication by inhibiting ethanol potentiation on GlyR. M554 is a recently discovered small molecule capable of binding to Gβγ with potent in vitro and in vivo inhibitory activity. This compound has been tested as a mixture of diastereomers, and no information is available concerning the stereospecific activity of each species, which is critical to pursue efforts on lead optimization and drug development. In this work, we explored the differential activity of four M554 stereoisomers by in silico molecular dynamics simulations and electrophysiological experiments. Our results revealed that the (R,R)-M554 stereoisomer is a promising lead compound that inhibits ethanol potentiation of GlyR.
