VU0357017 (hydrochloride)

1135242-13-5

C18H28ClN3O3

DMSO : >= 33 mg/mL (89.22 mM)

Neuronal Signaling; GPCR/G Protein

VU0357017 hydrochloride is a highly selective M1 agonists that appear to act at an allosteric site to activate the receptor (EC50 = 477 +/- 172 nM; pEC50 = 6.37 +/- 0.15). IC50 value: 477 +/- 172 nM (EC50) [1] Target: M1 in vitro: VU0357017 is a M1-selective agonists that appear to activate M1 through actions at an allosteric site. Ki values of VU0357017 derived from competition binding experiment is 9.91(rM1), 21.4 (rM2), 55.3 (rM3), 35 (rM4), and 50 (rM5), respectively. [1] VU0357017 is a potent and efficacious M1 agonist, selective versus M2 M5 family members and allosteric agonist. VU0357017 is a highly selective M1 agonist suggests that these compounds are unlikely to act at the highly conserved orthosteric site on M1 and are more likely to act as allosteric agonists. [2] VU0357017 has robust effects on M1-activation of calcium mobilization and ERK1/2 phosphorylation but have little effect on beta-arrestin recruitment. VU0357017 induces calcium release and ERK phosphorylation but is without effects on beta-arrestin recruitment. VU0357017 significantly enhances threshold theta-burst LTP and VU0364572 induces LTD at the Schaffer collateral-CA1 synapse of rodent hippocampal slices. [3] in vivo: VU0357017 has robust efficacy in improving hippocampal-dependent learning in rats. VU0357017 enhances performance in Morris water maze and contextual fear conditioning in rats. [3]