VU0364572 (trifluoroacetate salt)
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
IC50: 477 ± 172 nM
VU0364572 is a M1 agonist.
Alzheimer's disease (AD) is the leading cause of dementia worldwide, and no disease-modifying therapy is availables. Selective M1 muscarinic acetylcholine receptor activation is an attractive mechanism for AD therapy since M1 mediates key effects on cognition, memory, and behavior and has potential for disease-modifying effects on Aβ formation and tau phosphorylation.
In vitro: Previous study found that VU0364572 could completely displace [(3)H]-NMS binding to the orthosteric site of M(1)-M(5) receptors at high concentrations. Moreover, consistent with previous studies suggesting actions at a site that is distinct from the orthosteric binding site, VU0364572 was able to slow the rate of [(3)H]-NMS dissociation from CHO-rM(1) membranes [1].
In vivo: To validate M1 as a neuroprotective treatment target for AD, VU0364572 was chronically dosed to 5XFAD mice from a young age preceding Aβ pathology to an age where these mice are known to display memory impairments. Results showed that VU0364572 could significantly decrease oligomeric (oAβ) levels in the cortex, demonstrating one mechanism whereby VU0364572 might exert its neuroprotective effects by reducing the available oAβ pool in the brain. These findings suggested that chronic M1 activation has neuroprotective potential for preventing memory impairments and reducing neuropathology in AD [2].
Clinical trial: So far, no clinical study has been conducted.
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. Disease-Modifying Effects of M1 Muscarinic Acetylcholine Receptor Activation in an Alzheimer's Disease Mouse Model. ACS Chem Neurosci. 2017 Mar 7. doi: 10.1021/acschemneuro.6b00278.
Physical Appearance | A crystalline solid |
Storage | Store at -20°C |
M.Wt | 487.5 |
Cas No. | 1240514-89-9 |
Formula | C21H31N3O3·CF3COOH |
Solubility | ≤25mg/ml in ethanol;14mg/ml in DMSO;16mg/ml in dimethyl formamide |
Chemical Name | (3R)-3-[(2-methylbenzoyl)amino]-[1,4'-bipiperidine]-1'-carboxylic acid, ethyl ester, 2,2,2-trifluoroacetate |
SDF | Download SDF |
Canonical SMILES | CC1=C(C(N[C@@H]2CCCN(C3CCN(C(OCC)=O)CC3)C2)=O)C=CC=C1.OC(C(F)(F)F)=O |
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