Identification of GIRK2 channel modulators

National Center For Advancing Translational Sciences

Investigators

Abstract

The GIRK2 ion-channel was identified earlier as a potential target for treating addictions caused by alcohol and certain drugs. During the reporting period, the collaborative team worked to perform in silico screening of NCATS molecular libraries, using structural coordinates of GIRK channels. The homology model was utilized in the in silico screening of 120M molecule from the ZINC15 database. As a result of the screening, GIRK2 modulator candidates were identified. Subsequently, the activity of a number of candidates were confirmed in a fluorescence flux and electrophysiological assays, and key compounds will be evaluated in additional molecular modeling, electrophysiological and functional assays.