low cns exposure

ELN-441958 is a potent, neutral antagonist of the B1 receptor, inhibiting the binding of the B1 agonist ligand [3H]DAKD to IMR-90 cells with a Ki of 0.26 nM. ELN-441958 (ELN 441958) is highly selective for B1 over B2 receptors.

AM-3189 is a potent and selective GPR40 Agonist with minimal CNS penetration, superior pharmacokinetic properties and in vivo efficacy comparable to AMG 837. AM-3189 maintains the in vivo efficacy of AMG 837 while displaying a superior pharmacokinetic profile and minimal CNS exposure. Similar to AMG 837, while highly potent on GPR40, AM-3189 was highly selective over the closely related GPCRs, GPR41 and GPR43. 13kdemonstrated low clearance, moderate volume of distribution, and good oral bioavailability. AM-3189 does not penetrate the rat CNS as indicated by a rat brain to plasma ratio of 0.04 at 3 h after an oral dose of 5 mg/kg.