VU 0357017 hydrochloride (CID-25010775) 是一种有效的、选择性的、可穿透脑的 M1 毒蕈碱乙酰胆碱受体变构激动剂，EC50 为 477 nM。
| Cas No. | 1135242-13-5 |
| 别名 | CID-25010775 |
| 化学名 | ethyl 4-((2-(2-methylbenzamido)ethyl)amino)piperidine-1-carboxylate hydrochloride |
| Canonical SMILES | O=C(N1CCC(CC1)NCCNC(C2=CC=CC=C2C)=O)OCC.Cl |
| 分子式 | C18H27N3O3.HCl |
| 分子量 | 369.89 |
| 溶解度 | DMSO: 3 mg/ml,PBS (pH 7.2): 5 mg/ml |
| 储存条件 | Store at -20℃ |
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while. |
| Shipping Condition | Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request |
| 产品描述 | 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: M1in 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 β-arrestin recruitment. VU0357017 induces calcium release and ERK phosphorylation but is without effects on β-arrestin recruitment. VU0357017 significantly enhances threshold Θ-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] References:
[1]. Digby GJ, et al. Chemical modification of the M(1) agonist VU0364572 reveals molecular switches in pharmacology and a bitopic binding mode. ACS Chem Neurosci. 2012 Dec 19;3(12):1025-36.
[2]. Lebois EP, et al. Discovery and characterization of novel subtype-selective allosteric agonists for the investigation of M(1) receptor function in the central nervous system. ACS Chem Neurosci. 2010;1(2):104-121.
[3]. Digby GJ, et al. Novel allosteric agonists of M1 muscarinic acetylcholine receptors induce brain region-specific responses that correspond with behavioral effects in animal models. J Neurosci. 2012 Jun 20;32(25):8532-44.
[4]. Sheffler DJ, et al. Further exploration of M allosteric agonists: subtle structural changes abolish M allosteric agonism and result in pan-mAChR orthosteric antagonism. Bioorg Med Chem Lett. 2013 Jan 1;23(1):223-7. |
