GPR55 is a G protein-coupled receptor (GPCR) that is weakly activated by some cannabinoids (CBs) at nM concentrations but displays a 5- to 10-fold greater stimulation in response to 1 μM lysophosphatidylinositol (LPI). CID16020046 is a GPR55 inverse agonist that antagonizes GPR55 constitutive activity with an IC50 value of 15 μM. It inhibits GPR55-mediated ERK1/2 phosphorylation, LPI-induced Ca2+ signaling (IC50 = 0.21 μM in HEK-GPR55 cells), and GPR55-mediated transcription factor activation. It does not affect ERK1/2 phosphorylation or transcription factor activation in CB receptor expressing cells and demonstrates weak activity against a broad spectrum of other GPCRs, ion channels, kinases, and nuclear receptors. This compound has been shown to block GPR55-mediated endothelial wound healing and reverse LPI-inhibited platelet aggregation.
