TABLE 1

Potency and selectivity of vibegron at human, rhesus, rat, and dog β1, β2, and β3AR

Potency was measured using CHO cell lines stably expressing the appropriate receptor (Bmax 50–100 fmol/mg for β3AR cell lines, 300–500 fmol/mg for β1 and β2). To determine potency in the presence of serum, compounds were assayed in the presence of 40% autologous serum (pooled donors). EC50 for vibegron in the presence of 40% dog serum was not determined. Activation was determined relative to the known full agonist isoproterenol (1 μM). EC50 of isoproterenol at the human, rhesus monkey, rat, and dog β3AR receptors was 28, 12, 124, and 264 nM, respectively. Values represent geometric mean with confidence intervals (CI); N ≥ 6 for all values. β3AR potency has been previously described (Edmondson et al., 2016).

βAR SubtypeSpeciesEC50 (CI)EC50, nM w/ 40% Serum (CI)
nM% activation
β3Human1.0 (1.5,0.71); 84%1.5 (2.3, 1.0); 102%
β1Human>10,000; 5%
β2Human>10,000; 7%
β3Rhesus Monkey0.52 (0.81, 0.30); 108%5.5 (12, 2.6); 98%
β1Rhesus Monkey>10,000; 4%
β2Rhesus Monkey>10,000; 0%
β3Rat81 (119,55); 83%118 (161,85); 89%
β1Rat>10,000; 0%
β2Rat>10,000; 1%
β3Dog10 (15, 7.1); 82%N.D.
β1Dog>10000; 2%
β2Dog>10,000; 1%
  • N.D., not determined.