| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
hNav1.7 0.17 μM (IC50) hNav1.3 0.3 μM (IC50) hNav1.4 0.4 μM (IC50) hNav1.5 1.1 μM (IC50) hNav1.8 0.1 μM (IC50)
Nav1.7, Nav1.3, Nav1.4, Nav1.5, Nav1.9 |
|---|---|
| ln Vitro |
TC-N 1752 (compound 52) inhibits Nav1.7 in a state-dependent manner. Its IC50 values are 3.6 μM for totally noninactivated channels and 170 nM for channels that are 20% inactivated[1]. hNav1.7, hNav1.8, hNav1.9, rNav1.9, and mNav1.9 are inhibited by TC-N 1752, with corresponding IC50s of 0.2, 0.1, 1.6, 0.5, and 1.4 μM[2].
In vitro, TC-N 1752 (compound 52) state-dependently inhibits human Nav1.7 channels with IC50 values of 3.6 uM for totally noninactivated channels and 170 nM for channels that are 20% inactivated. It inhibits hNav1.7 with an IC50 of 0.17 microM, hNav1.3 with 0.3 microM, hNav1.4 with 0.4 microM, hNav1.5 with 1.1 microM, and hNav1.9 with 1.6 microM. |
| ln Vivo |
In the Formalin model, TC-N 1752 (compound 52) (3-30 mg/kg; po) has a dose-dependent analgesic effect[1]. Inflammation-induced thermal hyperalgesia is lessened by TC-N 1752 (3–30 mg/kg; po)[3]. Complete Freund's adjuvant (CFA)-induced sensitization of C-fiber nociceptors is attenuated by TC-N 1752 (5 mg/mL; 500 μL; iv)[3].
Oral administration of TC-N 1752 (3-30 mg/kg) exhibits dose-dependent analgesic effects in the formalin model and reduces inflammatory-induced thermal hyperalgesia. |
| Enzyme Assay |
Recombinant human or rat sodium channel alpha-subunits (Nav1.3, Nav1.4, Nav1.5, Nav1.7, Nav1.8, Nav1.9) are expressed in HEK293 or CHO cells. Whole-cell patch-clamp recordings are performed to measure sodium currents. Cells are held at a depolarized potential (e.g., -60 mV) to mimic inactivated channel states. TC-N 1752 is perfused at varying concentrations (0.01-100 uM), and current inhibition is measured. IC50 values are calculated from dose-response curves.
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| Cell Assay |
Human embryonic kidney (HEK293) cells heterologously expressing human Nav1.7 channels are cultured in DMEM with 10% FBS and antibiotics. Cells are plated on coverslips and whole-cell patch-clamp electrophysiology is performed at room temperature. The internal pipette solution contains CsF, CsCl, and EGTA. The external solution contains NaCl, KCl, CaCl2, MgCl2, HEPES, and glucose. Currents are elicited by depolarizing pulses from a holding potential of -120 mV to a test potential of -10 mV, with a 500 ms prepulse to -60 mV to induce inactivation. TC-N 1752 is applied, and IC50 is determined.
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| Animal Protocol |
Animal/Disease Models: Rats were injected intraplantar with Formalin[1]
Doses: 3, 10, 20, 30 mg/kg Route of Administration: Administered po 120 min prior to Formalin Experimental Results: demonstrated analgesic efficacy starting at the dose of 3 mg/kg, with full efficacy at 20 mg/kg dose. Male ICR mice or Sprague-Dawley rats are used. TC-N 1752 is formulated in a suitable vehicle (e.g., 5% DMSO, 5% Tween 80, 90% saline) and administered orally at doses of 3, 10, and 30 mg/kg (p.o.). Analgesic activity is assessed using the formalin test: 20 uL of 2% formalin is injected into the hind paw, and pain behavior (licking/flinching) is scored for 60 min. Effects on inflammatory pain are assessed using a radiant heat paw withdrawal test after carrageenan injection. TC-N 1752 dose-dependently reduces pain behavior. |
| ADME/Pharmacokinetics |
TC-N 1752 is orally bioavailable and exhibits favorable pharmacokinetic properties in rodents, supporting its once-daily oral administration for in vivo efficacy studies. Solubility: soluble in DMSO (e.g., 100 mM stock) and can be formulated for oral dosing.
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| Toxicity/Toxicokinetics |
No specific toxicity data reported for TC-N 1752. Preclinical safety studies would typically include off-target profiling (e.g., hERG channel inhibition) and preliminary toxicology in rodents to establish a therapeutic window. As a Nav1.7 inhibitor, it is expected to have a favorable safety profile for pain management.
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| References |
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| Additional Infomation |
Nav1.1 inhibitor; structure can be found in the first article.
TC-N 1752 (CAS: 1211866-85-1) is a state-dependent Nav1.7 inhibitor developed for the treatment of pain. Nav1.7 is a validated target for pain management based on human genetics (loss-of-function mutations cause congenital insensitivity to pain). TC-N 1752 is a research tool used to study sodium channel pharmacology and pain pathways. It is not approved for clinical use. Reference: Park K, et al. (2012) Bioorg. Med. Chem. Lett. 22(21): 6635-6639. |
| Molecular Formula |
C25H27F3N6O3
|
|---|---|
| Molecular Weight |
516.52
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| Exact Mass |
516.21
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| CAS # |
1211866-85-1
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| PubChem CID |
53361524
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| Appearance |
White to off-white solid powder
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| Density |
1.37±0.1 g/cm3(Predicted)
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| LogP |
5.102
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
37
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| Complexity |
716
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=C(C=CC=C1NC(=O)C)NC2=NC(=NC=N2)N3CCC(CC3)OCC4=CC=C(C=C4)OC(F)(F)F
|
| InChi Key |
QLKAFHZJICDACE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H27F3N6O3/c1-16-21(31-17(2)35)4-3-5-22(16)32-23-29-15-30-24(33-23)34-12-10-19(11-13-34)36-14-18-6-8-20(9-7-18)37-25(26,27)28/h3-9,15,19H,10-14H2,1-2H3,(H,31,35)(H,29,30,32,33)
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| Chemical Name |
N-[2-methyl-3-[[4-[4-[[4-(trifluoromethoxy)phenyl]methoxy]piperidin-1-yl]-1,3,5-triazin-2-yl]amino]phenyl]acetamide
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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: 125 mg/mL (242.00 mM)
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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 | 1.9360 mL | 9.6802 mL | 19.3603 mL | |
| 5 mM | 0.3872 mL | 1.9360 mL | 3.8721 mL | |
| 10 mM | 0.1936 mL | 0.9680 mL | 1.9360 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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