| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Targets |
(S)-LTGO-33 specifically inhibits the voltage-gated sodium channel NaV1.8. NaV1.8 is a subtype of sodium channels that is primarily expressed in peripheral sensory neurons (nociceptors). It plays a critical role in the generation and propagation of action potentials in pain-sensing neurons. By blocking NaV1.8, (S)-LTGO-33 decreases the excitability of these neurons, reducing the transmission of pain signals from the periphery to the central nervous system. This makes it a promising drug candidate for treating a wide range of pain disorders.
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| ln Vitro |
In vitro, (S)-LTGO-33 is characterized using electrophysiology techniques. Patch-clamp electrophysiology is the gold standard for measuring sodium channel inhibition. HEK293 cells stably expressing human NaV1.8 are used. Whole-cell currents are recorded in voltage-clamp mode. (S)-LTGO-33 is applied at increasing concentrations (1 nM-10 uM). The voltage-dependence of channel inhibition is assessed, and the half-maximal inhibitory concentration (IC₅0) is determined. While an exact IC₅0 for (S)-LTGO-33 is not provided, related NaV1.8 inhibitors typically have IC₅0 values in the nanomolar range. The compound is selective for NaV1.8 over other sodium channel subtypes (NaV1.2, NaV1.5, NaV1.7).
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| ln Vivo |
In vivo, (S)-LTGO-33 can be used for the treatment of pain disorders. Preclinical studies would typically involve rodent models of acute and chronic pain. In a mouse model of acute thermal pain (hot plate test), administration of (S)-LTGO-33 (e.g., 10-50 mg/kg, oral or IP) would produce a significant increase in latency to paw withdrawal, indicating an antinociceptive effect. In a model of neuropathic pain (e.g., chronic constriction injury of the sciatic nerve), chronic administration of (S)-LTGO-33 would produce a dose-dependent reversal of mechanical allodynia and thermal hyperalgesia, confirming its efficacy in treating pathological pain.
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| Enzyme Assay |
Non-cellular (enzymatic or receptor binding) assays for ion channels are not applicable; the functional readout is electrophysiology. However, radioligand binding assays for sodium channels can be performed. Membranes from HEK293 cells expressing NaV1.8 are incubated with a radiolabeled sodium channel toxin (e.g., [3H]saxitoxin or [3H]tetrodotoxin) in the presence of varying concentrations of (S)-LTGO-33. After incubation, bound radioactivity is collected by filtration and counted. The IC₅0 for displacing the radioligand is calculated. This assay measures the binding affinity of the compound to the channel. The selectivity over other sodium channel isoforms can be assessed by repeating the binding assay on membranes from cells expressing other NaV subtypes.
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| Cell Assay |
Cellular assays are electrophysiological. HEK293 cells stably expressing the human NaV1.8 channel are seeded onto coverslips. The next day, cells are subjected to whole-cell patch-clamp recording. The cells are held at -80 mV, and a series of depolarizing voltage steps (e.g., from -60 mV to +40 mV) are applied to activate the sodium channels. (S)-LTGO-33 is applied via a perfusion system at concentrations ranging from 0.1 nM to 10 uM. The peak inward sodium current is measured. The percent inhibition is calculated, and the IC₅0 is determined from the dose-response curve. To assess state-dependency, the protocol is repeated with varying holding potentials.
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| Animal Protocol |
A standard in vivo model for testing analgesic compounds is the formalin test in mice. Male C57BL/6 mice (n=8-10 per group) are injected with (S)-LTGO-33 (10, 30, 100 mg/kg) or vehicle (e.g., 10% DMSO/90% saline) orally or intraperitoneally. After 30-60 minutes, 20 uL of 2% formalin is injected into the right hind paw. The time spent licking/biting the injected paw is recorded in two phases: acute phase (0-5 min, direct activation of nociceptors) and tonic phase (15-30 min, inflammatory pain). A significant reduction in licking time in the tonic phase indicates an antinociceptive effect. A positive control (e.g., morphine, 5 mg/kg) is used for assay validation.
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| ADME/Pharmacokinetics |
(S)-LTGO-33 (MW 467.44, logP ~4) is a lipophilic small molecule. Good pharmacokinetic properties are predicted for NaV1.8 inhibitors intended for oral administration, including good oral bioavailability (F% >50%) and a plasma half-life (t1/2) of approximately 4-8 hours in rodents. It is expected to cross the blood-brain barrier (BBB) to a limited extent, as its primary site of action is peripheral sensory neurons. It is soluble in DMSO. For storage, the powder should be kept at -20degC, protected from light. For in vivo use, it can be formulated in 10% DMSO, 40% PEG300, 5% Tween 80, 45% saline.
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| Toxicity/Toxicokinetics |
The toxicological profile of (S)-LTGO-33 has not been fully disclosed. As a sodium channel blocker, potential side effects could include off-target activity on other NaV subtypes (e.g., NaV1.5 in cardiac tissue, which could affect cardiac conduction). Standard preclinical safety studies (e.g., hERG channel inhibition assay, subacute toxicity in rats) would be required for drug development. Standard safety precautions for research chemicals apply: wear gloves, lab coat, and goggles. Not for human consumption.
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| References | |
| Additional Infomation |
(S)-LTGO-33 (CAS 2241669-86-1) is a selective inhibitor of the voltage-gated sodium channel NaV1.8, a validated target for pain therapy. NaV1.8 is expressed in peripheral pain-sensing neurons and is a key mediator of pain signals. Selective NaV1.8 inhibitors have the potential to be non-addictive analgesics without the central side effects of opioids. This compound is for research use only and is not an FDA-approved drug.
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| Molecular Formula |
C21H17F4N3O3S
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| Molecular Weight |
467.44
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| Appearance |
Off-white to light yellow solid powder
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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 : ~200 mg/mL (~427.86 mM; with ultrasonication)
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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 | 2.1393 mL | 10.6966 mL | 21.3931 mL | |
| 5 mM | 0.4279 mL | 2.1393 mL | 4.2786 mL | |
| 10 mM | 0.2139 mL | 1.0697 mL | 2.1393 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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