ATR-258

ATR-258 is a GRK-biased agonist of the beta2-adrenergic receptor (beta2-AR). It binds to the orthosteric site on beta2-AR and mediates glucose uptake dependent on G protein-coupled receptor kinase 2 (GRK2) with low Galphas-dependent cAMP generation in a phenotypic screen. ATR-258 (10 µM) increases glucose uptake in L6 cells that endogenously express beta2-AR, an effect that can be blocked by the beta2-AR antagonist ICI 118551 (Cay15591) or the mTORC2 inhibitor JR-AB2-011. Oral administration of ATR-258 (0.3 mg/kg) improves glucose tolerance, reduces fat mass, and increases lean mass in diet-induced obese (DIO) mice without increasing heart weight. ATR-258 in combination with liraglutide (Cay24727) reduces fat mass without reducing lean mass in DIO mice.. SMILES: FC1=CC([C@H](CNC(C)(C)C)O)=CN=C1. InChi Code: InChI=1S/C11H17FN2O/c1-11(2,3)14-7-10(15)8-4-9(12)6-13-5-8/h4-6,10,14-15H,7H2,1-3H3/t10-/m0/s1. InChi Key: SASMSPQPEDQJII-JTQLQIEISA-N