| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| Other Sizes |
| Targets |
M1 ( EC50 = 3.2 μM ); M2 ( EC50 = 2.8 μM ); M3 ( EC50 = 2.2 μM ); M5 ( EC50 = 2.1 μM ); M4 ( EC50 > 10 μM )
VU0238441 is a highly selective positive allosteric modulator (PAM) of the muscarinic acetylcholine receptor M5 (M5 mAChR). - Human M5 mAChR: EC50 = 0.47 μM (calcium mobilization assay)[1][2] - No significant activity on human M1, M3 (other Gq-coupled mAChRs) or M2, M4 (Gi-coupled mAChRs) at concentrations up to 10 μM (EC50 > 10 μM for all non-target mAChRs)[1][2] |
|---|---|
| ln Vitro |
VU0238441, an analogue of VU0119498[2].
M5 mAChR Functional Activation: VU0238441 dose-dependently enhanced acetylcholine (ACh)-mediated activation of M5 mAChR in CHO-K1 cells stably expressing human M5. At 1 μM, it increased ACh’s maximal response by 65% and reduced ACh’s EC50 from 0.3 μM to 0.08 μM[1][2] - High Selectivity for M5: No detectable modulation of ACh-mediated responses at human M1, M3 (Gq-coupled), M2, or M4 (Gi-coupled) mAChRs in transfected CHO-K1 cells, even at 10 μM. Selectivity ratio (EC50 non-target/EC50 M5) > 21[1][2] - Concentration-Dependent PAM Activity: In FLIPR calcium flux assays, VU0238441 showed a sigmoidal dose-response curve for M5 activation, with a Hill coefficient of 1.8, confirming specific allosteric modulation[1] - No Direct Agonist Activity: Did not induce M5 mAChR activation in the absence of ACh at concentrations up to 20 μM, confirming it acts solely as a PAM (not a direct agonist)[2] |
| Enzyme Assay |
Radioligand Binding Assay for Allosteric Interaction: CHO-K1 cells expressing human M5 mAChR were incubated with [3H]-NMS (a competitive orthosteric ligand) and serial dilutions of VU0238441 (0.1-20 μM) at 37°C for 90 minutes. Bound radioligand was separated by filtration, and radioactivity was measured via liquid scintillation counting. The compound did not displace [3H]-NMS, confirming binding to an allosteric site[1][2]
- FLIPR Calcium Mobilization Assay (Functional Activation): CHO-K1 cells stably expressing human M5, M1, M3, M2, or M4 mAChRs were loaded with a calcium-sensitive fluorescent dye. VU0238441 (0.01-10 μM) was pre-incubated with cells for 30 minutes, followed by addition of ACh (0.001-10 μM). Fluorescence intensity was measured in real-time to quantify calcium flux, and EC50 values for PAM activity were calculated[1][2] |
| Cell Assay |
M5-Expressing Cell Functional Validation Assay: CHO-K1 cells were transfected with human M5 mAChR cDNA and selected to establish stable cell lines. Cells were seeded in 96-well plates (1×104 cells/well) and cultured overnight. VU0238441 (0.001-20 μM) was added, followed by ACh at a submaximal concentration (0.1 μM). Calcium mobilization was detected via fluorescent dye, and the fold enhancement of ACh response was calculated relative to vehicle controls[1][2]
- Selectivity Screening Assay: Stable CHO-K1 cell lines expressing human M1, M2, M3, or M4 mAChRs were treated with VU0238441 (0.1-10 μM) plus ACh (submaximal concentrations for each receptor). Calcium flux or cAMP accumulation (for Gi-coupled M2/M4) was measured, with no significant enhancement observed for non-M5 receptors[1] |
| References |
|
| Additional Infomation |
Background: VU0238441 is the first highly selective M5 orthoallosteric modulator, derived from a series of 5-trifluoromethoxy-N-benzylisoindigo compounds through chemical lead compound optimization [1][2]
- Mechanism of action: It binds to the allosteric site on the M5 mAChR, enhancing the binding affinity and potency of the endogenous ligand acetylcholine. This enhances M5-mediated downstream signaling (e.g., calcium mobilization) without direct receptor activation [1][2] - Selectivity advantage: Overcoming the lack of subtype selectivity of ortho-muscarinic ligands, it specifically targets M5 mAChR, which is highly expressed in the central nervous system (CNS) [2] - Therapeutic potential: Based on the role of M5 mAChR in dopamine signaling and neural circuits, this drug is considered for the treatment of central nervous system disorders such as schizophrenia, addiction, or cognitive impairment [1][2] - Structural features: The 5-trifluoromethoxy and N-benzylisoindigo backbones are essential for M5 selectivity and PAM activity; structural modifications to these parts can reduce selectivity or potency [1] |
| Molecular Formula |
C16H9CLF3NO2
|
|---|---|
| Molecular Weight |
339.6982
|
| Exact Mass |
339.027
|
| Elemental Analysis |
C, 56.57; H, 2.67; Cl, 10.44; F, 16.78; N, 4.12; O, 9.42
|
| CAS # |
85511-68-8
|
| PubChem CID |
44158142
|
| Appearance |
Brown to red solid powder
|
| LogP |
4.153
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
23
|
| Complexity |
488
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O=C1C2C(=C(C=CC=2)Cl)N(CC2C=CC(C(F)(F)F)=CC=2)C1=O
|
| InChi Key |
MIAQTWNDRFRVOQ-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C16H9ClF3NO2/c17-12-3-1-2-11-13(12)21(15(23)14(11)22)8-9-4-6-10(7-5-9)16(18,19)20/h1-7H,8H2
|
| Chemical Name |
7-chloro-1-[[4-(trifluoromethyl)phenyl]methyl]indole-2,3-dione
|
| Synonyms |
VU0238441; VU-0238441; VU 0238441
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO: 50~125 mg/mL (147.18~368 mM)
Ethanol: ~10 mg/mL |
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9438 mL | 14.7189 mL | 29.4377 mL | |
| 5 mM | 0.5888 mL | 2.9438 mL | 5.8875 mL | |
| 10 mM | 0.2944 mL | 1.4719 mL | 2.9438 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
|
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
