| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| 10mg |
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| 25mg | |||
| Other Sizes |
| Targets |
mAChR M5 (muscarinic acetylcholine receptor M5).
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|---|---|
| ln Vitro |
ML381 is a highly selective mAChR M5 orthosteric antagonist with an IC50 of 450 nM and a Ki of 340 nM. It has no inhibitory activity on mAChR M4 (IC50 > 30 µM). The compound is centrally nervous system penetrant. ML381 is unstable in rat plasma and can be mainly used as a molecular probe for in vitro and electrophysiological studies. It has overall acceptable DMPK properties in rat pharmacodynamic studies but poor metabolic stability.
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| ln Vivo |
The ideal use for ML381 (0.2 mg/kg; iv; single) is as an external/electrophysiological probe is because it contributes to poor stability and potential wastewater disposal in the tray, while having an overall DMPK profile in pesticide pharmacodynamic research.
ML381 has overall acceptable DMPK properties in rat pharmacodynamic studies but poor metabolic stability and undergoes amide hydrolysis in plasma. The compound is best suited as a molecular probe for in vitro and electrophysiological studies. It is centrally nervous system penetrant. Further optimization would be needed to improve metabolic stability for in vivo studies. |
| Enzyme Assay |
The in vitro receptor binding assay for mAChR M5 antagonism uses membrane preparations from cells expressing recombinant human mAChR M5. ML381 is incubated with the receptor preparation and a radiolabeled mAChR ligand (e.g., [3H]NMS) at varying concentrations (typically 0.1 nM to 100 µM). After incubation, bound and free radioactivity are separated by filtration. The Ki is calculated from competition binding curves. Selectivity is assessed by profiling against other mAChR subtypes (M1-M4).
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| Cell Assay |
In vitro cellular assays are performed using cells expressing recombinant mAChR M5 (e.g., CHO cells). Cells are treated with ML381 at concentrations ranging from 0.1 nM to 100 µM for 30-60 minutes. Receptor antagonism is assessed by measuring inhibition of agonist (e.g., acetylcholine or carbachol)-induced calcium mobilization or IP3 accumulation. The IC50 is calculated from dose-response curves. For electrophysiological studies, the effect of ML381 on M5-mediated currents is measured using patch-clamp techniques in oocytes or neuronal cells.
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| Animal Protocol |
Animal/Disease Models: SD (SD (Sprague-Dawley)) rat[1]. Acupuncture[1].
Doses: 0.2 mg/kg Route of Administration: intravenous; single. Experimental Results: 1.19 pharmacokinetic/PK/PK parameters of ML381 in SD (SD (Sprague-Dawley)) rats [1]. IV (0.2 mg/kg) Liver microsomes CLint (mL min-1 kg-1) 770 Predicted CLhep (mL min-1 kg-1) 64 fbrain 0.14 Cbrain/Cplasma (Kp*) 0.58 *Kp value determined at 0.25 hrs (hrs (hours)) After 0.2 mg/kg IV dose (n=2). In vivo animal model data for ML381 is limited due to its instability in rat plasma. The compound has overall acceptable DMPK properties in rat pharmacodynamic studies but poor metabolic stability and undergoes amide hydrolysis in plasma. It is best suited as a molecular probe for in vitro and electrophysiological studies. For in vivo studies, the compound would need to be administered via routes that avoid first-pass metabolism or with metabolic stabilization strategies. |
| ADME/Pharmacokinetics |
ML381 has a molecular weight of 379.42 g/mol and molecular formula C21H21N3O4. It is centrally nervous system penetrant. The compound is unstable in rat plasma and undergoes amide hydrolysis. It is soluble in DMSO and should be stored as a powder at -20°C. Pharmacokinetic parameters such as oral bioavailability, plasma half-life, and tissue distribution have been characterized but show poor metabolic stability. The compound is typically used in in vitro assays at concentrations ranging from nanomolar to low micromolar.
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| Toxicity/Toxicokinetics |
No detailed toxicity data is publicly available for ML381. As a research compound, it is not intended for human use and has not undergone formal toxicological evaluation. Standard preclinical safety assessments for mAChR antagonists would typically include selectivity profiling against a panel of mAChR subtypes and related GPCRs, hERG channel inhibition for cardiac safety, and CYP450 enzyme inhibition for drug-drug interaction potential. The compound is supplied as a solid and should be stored desiccated at -20°C.
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| References | |
| Additional Infomation |
ML381 is a research-grade mAChR M5 antagonist that is centrally nervous system penetrant. It is not approved for clinical use. The compound is also known as VU0488130. It is unstable in rat plasma and best suited as a molecular probe for in vitro and electrophysiological studies. ML381 has no inhibitory activity on mAChR M4 (IC50 > 30 µM). It is supplied as a solid with high purity and should be stored desiccated at -20°C.
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| Molecular Formula |
C21H21N3O4
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|---|---|
| Molecular Weight |
379.409145116806
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| Exact Mass |
379.153
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| CAS # |
1623481-80-0
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| PubChem CID |
42519285
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| Appearance |
Colorless to light yellow ointment
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| LogP |
2.2
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
28
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| Complexity |
544
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C[C@@H](C1=CC=CC=N1)N(C)C(=O)C2=NOC(=C2)COC3=CC=CC(=C3)C(=O)C
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| InChi Key |
JMYDHMCYZKRDPD-AWEZNQCLSA-N
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| InChi Code |
InChI=1S/C21H21N3O4/c1-14(19-9-4-5-10-22-19)24(3)21(26)20-12-18(28-23-20)13-27-17-8-6-7-16(11-17)15(2)25/h4-12,14H,13H2,1-3H3/t14-/m0/s1
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| Chemical Name |
5-[(3-acetylphenoxy)methyl]-N-methyl-N-[(1S)-1-pyridin-2-ylethyl]-1,2-oxazole-3-carboxamide
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| Synonyms |
ML 381ML-381 VU0488130 VU-0488130 ML381
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~263.57 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.59 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.59 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.59 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6357 mL | 13.1784 mL | 26.3567 mL | |
| 5 mM | 0.5271 mL | 2.6357 mL | 5.2713 mL | |
| 10 mM | 0.2636 mL | 1.3178 mL | 2.6357 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.
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