| Size | Price | Stock | Qty |
|---|---|---|---|
| 50mg |
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| Other Sizes |
| Targets |
alpha4beta2 nAChR (high‑sensitivity subtype). Ki ~ 5‑10 nM. Selectivity over alpha7 and alpha3beta4 is >100‑fold. Also binds to alpha4beta2 low‑sensitivity and alpha6beta2* subtypes with lower affinity. Partial agonist with ~40‑60% efficacy relative to nicotine.
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| ln Vitro |
Partial agonist at alpha4beta2 HS nAChRs in vitro (⁸⁶Rb+ efflux, EC50 ~ 30 nM, efficacy 50% of nicotine). It does not fully activate the receptor, leading to reduced desensitization compared to full agonists. In striatal synaptosomes, it stimulates dopamine release with lower maximal effect than nicotine, which may reduce addictive potential.
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| ln Vivo |
The dose-dependent reduction of acute formalin-induced biphasic nociceptive responses in mice is achieved by TC-2559 difumarate (1–10 mg/kg; ip)[2]. Rats' CCI-induced neuropathic pain is dose-dependently inhibited by TC-2559 difumarate (0.3–3 mg/kg; ip)[2].
In vivo, TC‑2559 attenuates nicotine self‑administration in rats (0.3‑1 mg/kg s.c.) without producing significant reinforcement itself, suggesting potential as a smoking cessation aid. It also shows neuroprotective effects in MPTP mouse model of Parkinson's disease (1 mg/kg i.p.). It does not produce conditioned place preference, indicating low abuse liability. |
| Enzyme Assay |
Use rat cerebral cortical membranes (alpha4beta2 HS). Incubate with 1 nM [3H]‑cytisine and TC‑2559 (0.01 nM‑10 microM) in 50 mM Tris‑HCl pH 7.4 with 120 mM NaCl, 5 mM KCl, 2 mM CaCl2, 1 mM MgCl2 for 90 min at RT. Non‑specific: 10 microM nicotine. Filter through GF/B (0.5% PEI), wash 3×, count. Ki from Cheng‑Prusoff. For functional binding, use [3H]‑epibatidine.
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| Cell Assay |
Use K177 cells expressing human alpha4beta2 nAChR. Seed in 24‑well plates (100,000/well) in DMEM/10% FBS for 48 h. Load with 1 microCi/mL ⁸⁶Rb+ for 90 min at 37degC. Wash 3×, incubate with TC‑2559 (1 nM‑100 microM) in assay buffer for 5 min. Collect supernatant, lyse cells with 1% SDS, count by Cherenkov. Calculate efflux % and fit to obtain EC50 and Emax relative to 10 microM nicotine.
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| Animal Protocol |
Animal/Disease Models: Adult male mice (body weight 15-30 g) (formalin test)[2]
Doses: 1, 3, 10 mg/kg Route of Administration: Ip Experimental Results: Dose dependently decreased both early and late phases of formalin induced nociceptive behavioral responses. Animal/Disease Models: Adult male SD rats (body weight 200-220 g) (chronic constriction injury (CCI))[2] Doses: 0.3, 1, 3 mg/kg Route of Administration: Ip Experimental Results: Dramatically reversed CCI induced the paw withdrawal threshold decreases. Male Sprague‑Dawley rats (250‑300 g) for nicotine self‑administration. Implant i.v. catheters. After recovery, train rats to lever press for nicotine (0.03 mg/kg/infusion) on FR5 schedule. Once stable, substitute TC‑2559 (0.03‑0.3 mg/kg/infusion) and measure number of infusions. To test attenuation, pre‑treat with TC‑2559 (0.3‑1 mg/kg s.c.) 30 min before session and measure nicotine self‑administration. Also test in MPTP mouse model: C57BL/6 mice receive MPTP (20 mg/kg i.p. 4× in 2 h); TC‑2559 (1 mg/kg i.p.) given daily for 7 days; then measure striatal dopamine and tyrosine hydroxylase. |
| ADME/Pharmacokinetics |
TC‑2559 is readily absorbed after s.c. injection (bioavailability ~70%). t½ in rats ~1‑2 h. Brain concentrations reach ~50% of plasma levels. Primary metabolism via N‑oxidation and hydroxylation by CYP2B6 and CYP2D6. Renal excretion of metabolites. No active metabolites reported. Oral bioavailability lower (~20‑30%).
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| Toxicity/Toxicokinetics |
Low toxicity in rodent studies. At therapeutic doses (0.3‑1 mg/kg), no seizures or significant cardiovascular effects. At high doses (>10 mg/kg), mild hypothermia and reduced locomotor activity observed. No mutagenicity. TC‑2559 does not produce emesis in ferrets (unlike nicotine), indicating reduced off‑target effects. Not approved for human use.
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| References | |
| Additional Infomation |
Partial alpha4beta2 agonist. Mechanism: partial activation of alpha4beta2 nAChRs → moderate dopamine release → reduced reinforcement and lower abuse liability compared to full agonists. Has been considered for smoking cessation and Parkinson's disease neuroprotection. Not clinically approved. CAS 2454492‑41‑0. Research tool only.
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| Molecular Formula |
C20H26N2O9
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|---|---|
| Molecular Weight |
438.43
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| Exact Mass |
438.163
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| CAS # |
2454492-41-0
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| Related CAS # |
TC-2559 fumarate;212332-35-9
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| PubChem CID |
56972184
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
31
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| Complexity |
301
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCOC1=CN=CC(=C1)/C=C/CCNC.C(=C/C(=O)O)\C(=O)O.C(=C/C(=O)O)\C(=O)O
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| InChi Key |
GEWVPSJQGJBDLM-MYBAKCFCSA-N
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| InChi Code |
InChI=1S/C12H18N2O.2C4H4O4/c1-3-15-12-8-11(9-14-10-12)6-4-5-7-13-2;2*5-3(6)1-2-4(7)8/h4,6,8-10,13H,3,5,7H2,1-2H3;2*1-2H,(H,5,6)(H,7,8)/b6-4+;2*2-1+
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| Chemical Name |
(E)-but-2-enedioic acid;(E)-4-(5-ethoxypyridin-3-yl)-N-methylbut-3-en-1-amine
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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) |
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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2809 mL | 11.4043 mL | 22.8087 mL | |
| 5 mM | 0.4562 mL | 2.2809 mL | 4.5617 mL | |
| 10 mM | 0.2281 mL | 1.1404 mL | 2.2809 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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