VU6000918 is a muscarinic acetylcholine (M4) positive allosteric modulator, with an EC50 of 19 nM for hM4[1].
VU6000918 demonstrates statistically significant AHL reversal (18%) from a low oral dose of 0.03 mg/kg and reaches maximal reversal (74%) from a 3 mg/kg dose, with a resulting in vivo plasma EC50 of 74 nM (0.66 nM unbound) based on terminal concentrations measured in the study animals (1.5 hr post-administration of 17j)[1].
[1]. James C Tarr, et al. Challenges in the development of an M 4 PAM preclinical candidate: The discovery, SAR, and in vivo characterization of a series of 3-aminoazetidine-derived amides. Bioorg Med Chem Lett. 2017 Jul 1;27(13):2990-2995.