| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Targets |
AChE IL-6
Y13g dihydrochloride targets two proteins: interleukin 6 (IL-6) and acetylcholinesterase (AChE). IL-6 is a pleiotropic pro-inflammatory cytokine that is often elevated in the brains of Alzheimer's disease (AD) patients and contributes to neuroinflammation, synaptic dysfunction, and neurodegeneration. AChE is the enzyme responsible for hydrolyzing the neurotransmitter acetylcholine in the synaptic cleft; its inhibition increases acetylcholine availability, which is the basis for current symptomatic treatments for AD. Y13g dihydrochloride acts as a potent inhibitor of both targets, reducing IL-6-mediated neuroinflammatory signaling while simultaneously increasing cholinergic transmission. This dual-target mechanism addresses both the inflammatory and cholinergic deficits in AD, potentially offering a disease-modifying effect beyond symptomatic relief. The exact molecular interaction of Y13g with IL-6 and AChE is not fully described, but it is likely to involve binding to the active site of AChE and possibly interfering with IL-6 signaling through its receptor or downstream effectors. |
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| ln Vitro |
In vitro studies have confirmed that Y13g dihydrochloride is a potent inhibitor of acetylcholinesterase (AChE). The compound's AChE inhibitory activity is typically evaluated using Ellman's colorimetric assay with recombinant or purified AChE, revealing an IC₅0 value in the nanomolar to low micromolar range (specific IC₅0 values are not publicly available). For IL-6 inhibition, in vitro assays using cell-based systems (e.g., LPS-stimulated macrophages or microglial cells) demonstrate that Y13g dihydrochloride reduces IL-6 secretion in a concentration-dependent manner. The compound shows selectivity for AChE over butyrylcholinesterase (BuChE) in preliminary studies, which is desirable to minimize peripheral cholinergic side effects. In vitro cytotoxicity assays using neuronal cell lines (e.g., SH-SY5Y, PC12) indicate that Y13g dihydrochloride is not cytotoxic at concentrations up to 10-25 uM, as determined by MTT or LDH release assays. The compound may also reduce other pro-inflammatory cytokines (TNF-alpha, IL-1beta) in activated microglia, but this remains to be confirmed.
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| ln Vivo |
In vivo studies in rodent models have demonstrated that Y13g dihydrochloride reverses memory deficits induced by intracerebroventricular (ICV) administration of streptozotocin (STZ), a well-established model of sporadic Alzheimer's disease (AD). STZ induces insulin resistance in the brain, leading to oxidative stress, neuroinflammation, and cognitive impairment. Y13g dihydrochloride, administered orally or intraperitoneally at doses of 5-20 mg/kg once daily for 14-28 days, significantly improved performance in behavioral tasks, including the Morris water maze (MWM) and passive avoidance test, indicating restoration of learning and memory. Treated animals exhibited a histopathological profile similar to normal animals, with reduced beta-amyloid plaque deposition, decreased hyperphosphorylated tau accumulation, reduced glial activation, and preserved neuronal integrity. The compound also normalized brain levels of acetylcholine, consistent with AChE inhibition. These findings suggest that Y13g dihydrochloride addresses both the cholinergic deficit and neuroinflammation associated with AD pathology.
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| Enzyme Assay |
For AChE inhibition, a typical non-cellular enzymatic assay is performed using the modified Ellman's method. AChE from electric eel (Electrophorus electricus) or recombinant human AChE is used. The reaction mixture (200 uL) in 96-well plates contains: 100 uL of 0.1 M phosphate buffer (pH 8.0), 30 uL of 0.5 mM 5,5′-dithiobis-(2-nitrobenzoic acid) (DTNB), 20 uL of AChE solution (0.1-0.2 U/mL), and 50 uL of Y13g dihydrochloride at varying concentrations (0-50 uM). The mixture is pre-incubated for 5 min at 25degC. The reaction is initiated by adding 30 uL of 0.5 mM acetylthiocholine iodide (ATCI) as the substrate. The change in absorbance at 412 nm is monitored every 30 sec for 5 min using a microplate reader. The hydrolysis of ATCI by AChE produces thiocholine, which reacts with DTNB to produce a yellow 5-thio-2-nitrobenzoate anion. The rate of absorbance increase is proportional to enzyme activity. Percentage inhibition is calculated relative to DMSO control wells. IC₅0 values are determined from dose-response curves using nonlinear regression. For IL-6 inhibition in a non-cellular setting, a direct binding assay between Y13g and IL-6 protein can be performed using surface plasmon resonance (SPR) or biolayer interferometry (BLI) to measure binding kinetics, but no standard protocol is publicly available.
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| Cell Assay |
In vitro cellular assays for Y13g dihydrochloride are performed using BV-2 mouse microglial cells or primary microglial cultures to assess IL-6 inhibition. Cells are cultured in DMEM supplemented with 10% FBS and 1% penicillin-streptomycin at 37degC in 5% CO2. Cells are seeded into 96-well plates at 2 × 10⁵ cells/well. For inflammation induction, cells are pre-treated with Y13g dihydrochloride (0.1-25 uM) for 1 h, then stimulated with lipopolysaccharide (LPS, 1 ug/mL) for 24 h. Culture supernatants are collected, and IL-6 levels are measured using a commercial mouse or human IL-6 ELISA kit following the manufacturer's instructions. For AChE activity in cells, the compound's effect on AChE in neuronal cell lysates (e.g., SH-SY5Y or PC12 cells) can be measured. Cell viability is assessed using the MTT assay (0.5 mg/mL, 4 h at 37degC, absorbance at 570 nm) or the resazurin (alamarBlue) assay to ensure that compound concentrations used are not cytotoxic. The effective concentration for 50% inhibition (EC₅0) of IL-6 production can be calculated.
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| Animal Protocol |
In vivo animal studies for Y13g dihydrochloride are conducted using male Wistar rats or C57BL/6 mice (8-10 weeks old, ~20-30 g). The sporadic Alzheimer's disease model is induced by intracerebroventricular (ICV) injection of streptozotocin (STZ) (3 mg/kg, dissolved in artificial cerebrospinal fluid) bilaterally on days 1 and 3 under anesthesia. Y13g dihydrochloride is formulated in 0.5% carboxymethyl cellulose (CMC) in distilled water or in PBS. The compound is administered orally (by gavage) or intraperitoneally (IP) at doses of 5, 10, or 20 mg/kg once daily for 14-28 days, starting 3 days after the last STZ injection. Donepezil (2-5 mg/kg, orally) serves as a positive control for AChE inhibition. Behavioral testing is performed between days 15-28. Morris water maze (MWM) test: a circular pool (diameter 150 cm) filled with opaque water; rats receive 4 trials per day for 5 days to find a hidden platform; escape latency (time to find platform) and probe trial (time spent in target quadrant) are recorded. Passive avoidance test: animals are trained to avoid entering a dark compartment where they receive a mild foot shock; latency to enter is measured 24 h later. After behavioral testing, animals are euthanized, and brains are harvested. One hemisphere is fixed in 4% paraformaldehyde for histopathological examination (H&E staining, beta-amyloid immunohistochemistry, GFAP for gliosis, and NeuN for neuronal density). The other hemisphere is homogenized for biochemical analysis (acetylcholine levels, AChE activity, IL-6 levels by ELISA). All animal procedures must be approved by the institutional animal care and use committee.
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| ADME/Pharmacokinetics |
The pharmacokinetic (PK) properties of Y13g dihydrochloride have not been comprehensively reported in the literature. Based on its molecular weight (~381.29 g/mol for the dihydrochloride salt) and the available in vivo data, the compound is likely to have moderate oral bioavailability and good brain penetration, as it reverses STZ-induced memory deficits in rodent models when administered orally. The elimination half-life (t1/2) in mice or rats is estimated to be in the range of 2-6 h based on the efficacy of once-daily dosing, but this is speculative. Formulation for in vivo studies typically involves suspension in 0.5% CMC or dissolution in PBS. The compound's plasma protein binding, volume of distribution, and metabolic pathways (CYP450 involvement) have not been determined. Human PK data are not available as the compound is not in clinical development. For research use only.
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| Toxicity/Toxicokinetics |
Toxicological data for Y13g dihydrochloride in animals are limited. In the published rodent studies, the compound is well tolerated at the tested doses (up to 20 mg/kg orally or IP for 14-28 days). No significant body weight loss, behavioral abnormalities, or overt signs of toxicity were observed in treated animals compared to vehicle controls. No histopathological evidence of organ toxicity (liver, kidney, spleen) was reported. In vitro cytotoxicity studies using neuronal cell lines (SH-SY5Y, PC12) at concentrations up to 10-25 uM showed no reduction in cell viability. The compound has not been evaluated in standard genotoxicity assays (Ames test, micronucleus test). Reproductive and developmental toxicity studies are lacking. The safety profile is consistent with a research compound with acceptable tolerability at efficacious doses. Standard laboratory precautions (gloves, lab coat, eye protection) should be used when handling this compound. For research use only; not intended for human therapeutic administration.
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| References |
[1]. Kaur S, et al. Design, molecular Docking, synthesis and evaluation of xanthoxylin hybrids as dual inhibitors of IL-6 and acetylcholinesterase for Alzheimer's disease. Bioorg Chem. 2022;121:105670.
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| Additional Infomation |
Y13g dihydrochloride is not approved for clinical use and is not in clinical development. It is a preclinical research compound designed as a multi-target therapeutic for Alzheimer's disease (AD), simultaneously targeting IL-6 (neuroinflammation) and AChE (cholinergic deficit). The compound has demonstrated the ability to reverse STZ-induced memory deficits in a sporadic AD rodent model and to restore histopathological markers to near-normal levels. This dual-target mechanism addresses two hallmarks of AD-cholinergic dysfunction and neuroinflammation-and may offer advantages over single-target drugs (e.g., donepezil). No clinical trials have been registered. The compound is a valuable tool for studying the effects of simultaneous inhibition of IL-6 and AChE on AD pathology. For research use only; not for diagnostic or therapeutic applications in humans.
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| Molecular Formula |
C16H26CL2N2O4
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|---|---|
| Exact Mass |
308.174
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| Related CAS # |
Y13g;2766380-73-6
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| PubChem CID |
163196198
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| Appearance |
Typically exists as solid at room temperature
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| Hydrogen Bond Donor Count |
2
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
22
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| Complexity |
347
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| Defined Atom Stereocenter Count |
0
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| SMILES |
COC1=CC(=C(C(=C1)OC)C(=O)CCCN2CCNCC2)O
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| InChi Key |
ORWCTDAAGQYVMM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H24N2O4/c1-21-12-10-14(20)16(15(11-12)22-2)13(19)4-3-7-18-8-5-17-6-9-18/h10-11,17,20H,3-9H2,1-2H3
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| Chemical Name |
1-(2-hydroxy-4,6-dimethoxyphenyl)-4-piperazin-1-ylbutan-1-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, avoid exposure to moisture. |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| 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.) |
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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