MS47134 is a potent, selective MRGPRX4 agonist with EC50 of 149 nM.
MS47134 displays 47-fold improved selectivity for MRGPRX4 over the Kir6.2/SUR1 potassium channel.
Off-target profiling of MS47134 at 320 GPCRs showed activity only at MRGPRX4 and MRG-PRX1 with no appreciable agonist or antagonist activity at the other 318 tested GPCRs.
MS47134 binds to MRGP RX4 on the extrac ellular side far from t he canonical to ggle switch W6.48 in 5-HT2AR.
A Y130ICL2A mutation reduced the agonist potency of MS47134 while the Y137ICL2A mutation in MRG-PRX2 has little effect.
