This probe was identified through an innovative approach to first screen a set of compounds using PRESTO-Tango, then using these results to refine a structural model that could be used for subsequent docking studies with a large set of compounds. These efforts have led to a probe is quite structurally novel relative to other GPCR ligands, has extremely high selectivity against a large collection of GPCRs as well as a broad panel of 76 kinases, and is active in an orthogonal cell assay. Another key attribute is that it possesses an inactive enantiomer, which can be used as an inactive probe. The deficiencies of the probe are its relatively modest cellular functional potency (740 nM), the lack of a binding data (Kd) to the receptor, and lack of ADME/PK data to guide in vivo use.
19 May 2020 )