Functional
profiling of ML321 against an array of 168 known GPCRs.
A single high concentration (10 μM) of ML321 was screened using
a β-arrestin recruitment assay in the DiscoverX gpcrMAX assay
panel in both antagonist (A) or agonist (B) modes as described in
the Methods. Data represent the percent maximum stimulation (agonist
mode) observed by a reference agonist for each GPCR or the percent
inhibition (antagonist mode) of a response produced by an EC80 concentration of a reference agonist for each GPCR. A complete key
to the GPCR array and numerical results are provided in Table S2. Only responses that deviated >20%
from
the baseline are considered to be significant. In panel (A), these
include the following receptors (% activity): D2RL (98%),
D2RS (98%), D3R (72%), 5-HT2A (48%), 5-HT2C (35%), BLT1 (leukotriene B4) (LTB4R) (37%), sphingosine-1-phosphate
4 (S1PR4) (36%), α2C-adrenergic (31%); and in panel
(B), CB2 cannabinoid (44%).