| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Targets |
Serine Hydrolase inhibitor-21 targets the serine hydrolase enzyme butyrylcholinesterase (BuChE). It acts as a direct inhibitor, binding to the active site of the enzyme and preventing the hydrolysis of its natural substrates, including the neurotransmitter acetylcholine and other choline esters. The compound exhibits a dissociation constant (Ki) of 429 nM for BuChE. It may also inhibit other serine hydrolases, but shows selectivity for BuChE over acetylcholinesterase (AChE), making it useful for dissecting the specific contributions of BuChE in neurological disease models.
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| ln Vitro |
In vitro, Serine Hydrolase inhibitor-21 shows potent inhibition of human butyrylcholinesterase (BuChE) with a Ki value of 429 nM. The inhibition kinetics are characterized by a reversible inhibition mechanism. The compound likely binds to the active site serine residue of BuChE, preventing access of the natural substrate. Its selectivity for BuChE over acetylcholinesterase (AChE) makes it a valuable tool for investigating the specific role of BuChE in cholinergic signaling and disease progression in conditions such as Alzheimer's disease, where BuChE activity increases as AChE declines.
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| ln Vivo |
In vivo studies for Serine Hydrolase inhibitor-21 are limited, but the compound shows promise as a research tool for Alzheimer's disease. BuChE inhibition in vivo would be expected to increase brain acetylcholine levels, potentially improving cognitive function. However, the blood-brain barrier permeability of this specific inhibitor has not been characterized. The compound may be used in animal models of Alzheimer's disease to evaluate the therapeutic potential of BuChE-selective inhibition. Further in vivo studies are needed to fully characterize its efficacy and CNS penetration.
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| Enzyme Assay |
BuChE inhibition assay (cell-free): Human recombinant butyrylcholinesterase (BuChE) enzyme is preincubated with varying concentrations of Serine Hydrolase inhibitor-21 (e.g., 0.1-10000 nM) and the chromogenic substrate butyrylthiocholine (0.1-1 mM) in the presence of Ellman's reagent (5,5'-dithiobis-(2-nitrobenzoic acid), DTNB). The reaction is monitored spectrophotometrically at 412 nm for 5-30 minutes at 25degC or 37degC. The rate of product formation is measured, and Ki values are calculated from Dixon plots or nonlinear regression analysis of dose-response curves.
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| Cell Assay |
Cell-based BuChE inhibition assay: Cells expressing butyrylcholinesterase (e.g., SH-SY5Y neuroblastoma cells or primary neurons) are seeded in 96-well plates. Cells are treated with Serine Hydrolase inhibitor-21 at various concentrations (e.g., 0.1-1000 microM) for 1-4 hours. After treatment, cells are lysed, and BuChE activity is measured using butyrylthiocholine as substrate and Ellman's reagent. Alternatively, culture media containing secreted BuChE can be assayed directly. The IC50 for BuChE inhibition in the cellular context is determined by comparing activity to untreated controls.
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| Animal Protocol |
In vivo animal protocol for BuChE inhibition studies: Mice or rats are administered Serine Hydrolase inhibitor-21 via intraperitoneal (i.p.) or oral (p.o.) route (typical doses 1-30 mg/kg). At various time points (0.5-24 hours post-dose), animals are euthanized, and brain and blood samples are collected. Brain homogenates and plasma are assayed for BuChE activity using the butyrylthiocholine/DTNB method. The percentage of BuChE inhibition is calculated relative to vehicle-treated controls to determine the in vivo potency and duration of action.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of Serine Hydrolase inhibitor-21 have not been fully characterized. Based on its molecular weight (320.37 g/mol) and lipophilicity (phenothiazine core), the compound is expected to have moderate to high membrane permeability and may penetrate the blood-brain barrier, a desirable property for CNS targets. The compound shows good solubility in DMSO (10-12 mg/mL) for formulation purposes. Metabolism likely involves oxidation of the phenothiazine sulfur and aromatic hydroxylation, followed by conjugation. Plasma half-life has not been reported.
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| Toxicity/Toxicokinetics |
Specific toxicity studies for Serine Hydrolase inhibitor-21 have not been published. As an experimental research compound, its safety profile is not well characterized. Based on its mechanism as a cholinesterase inhibitor, potential adverse effects may include cholinergic overstimulation (e.g., nausea, vomiting, diarrhea, bradycardia, excessive salivation, muscle weakness, and convulsions) if off-target inhibition of acetylcholinesterase occurs or if BuChE inhibition is excessive. However, these effects are theoretical and have not been reported in the literature for this specific compound. Standard laboratory safety precautions should be followed.
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| References |
[1]. Sultan Darvesh, et al. Novel pyridones and their use as modulators of serine hydrolase enzymes. WO2001077078A1.
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| Additional Infomation |
Serine Hydrolase inhibitor-21 is not a drug and has no clinical applications or regulatory approval. It is a research tool for studying the role of butyrylcholinesterase (BuChE) in cholinergic neurotransmission and neurodegenerative diseases, particularly Alzheimer's disease. As BuChE activity increases in the Alzheimer's brain while AChE declines, selective BuChE inhibitors represent a potential therapeutic strategy. This compound provides a means to investigate the therapeutic potential of BuChE-selective inhibition in preclinical models. Not for human use.
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| Molecular Formula |
C18H12N2O2S
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|---|---|
| Molecular Weight |
320.365082740784
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| Exact Mass |
320.061
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| CAS # |
366448-34-2
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| PubChem CID |
9836747
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| Appearance |
White to off-white solid powder
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| LogP |
2.6
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
23
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| Complexity |
549
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC=C2C(=C1)N(C3=CC=CC=C3S2)C(=O)C4=CNC(=O)C=C4
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| InChi Key |
FRWOZZSGXZOOSM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H12N2O2S/c21-17-10-9-12(11-19-17)18(22)20-13-5-1-3-7-15(13)23-16-8-4-2-6-14(16)20/h1-11H,(H,19,21)
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| Chemical Name |
5-(phenothiazine-10-carbonyl)-1H-pyridin-2-one
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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: 12 mg/mL (37.46 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.2 mg/mL (3.75 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 12.0 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: ≥ 1.2 mg/mL (3.75 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 12.0 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: ≥ 1.2 mg/mL (3.75 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 | 3.1214 mL | 15.6070 mL | 31.2139 mL | |
| 5 mM | 0.6243 mL | 3.1214 mL | 6.2428 mL | |
| 10 mM | 0.3121 mL | 1.5607 mL | 3.1214 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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