| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
The parent compound, Acoltremon, targets the TRPM8 (Transient Receptor Potential Melastatin 8) ion channel, which is a cold-sensitive receptor. Activation of TRPM8 produces a cooling sensation and has been shown to have analgesic effects in models of chronic neuropathic pain. In the eye, TRPM8 activation promotes tear production. Acoltremon is a potent and selective TRPM8 agonist (EC₅0 = 39 nM). The deuterated internal standard has the same target but is used only for analytical purposes.
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| ln Vitro |
Stable heavy isotopes of hydrogen, carbon, and other elements have been incorporated into drug molecules, largely as tracers for quantitation during the drug development process. Studies involving the human use of drugs labeled with deuterium suggest that these compounds may offer some advantages when compared with their nondeuterated counterparts. Deuteration has gained attention because of its potential to affect the pharmacokinetic and metabolic profiles of drugs. Deutetrabenazine is the first deuterated drug to receive Food and Drug Administration approval. This deuterated form of the drug tetrabenazine is indicated for the treatment of chorea associated with Huntington's disease as well as tardive dyskinesia. Ongoing clinical trials suggest that a number of other deuterated compounds are being evaluated for the treatment of human diseases and not merely as research tools.
The parent compound, Acoltremon, is a potent TRPM8 agonist with an EC₅0 of 39 nM in a calcium flux assay using cells expressing human TRPM8. In vivo, it produces a dose-dependent analgesic effect in chronic neuropathic pain models. The deuterated internal standard is not used in biological activity assays. In an MTT assay using HepG2 cells, Acoltremon-d3 is non-toxic (IC₅0 >100 uM). |
| ln Vivo |
Deuterated compounds may, in some cases, offer advantages over nondeuterated forms, often through alterations in clearance. Deuteration may also redirect metabolic pathways in directions that reduce toxicities. The approval of additional deuterated compounds may soon follow. Clinicians will need to be familiar with the dosing, efficacy, potential side effects, and unique metabolic profiles of these new entities.
In vivo, the parent compound (Acoltremon, also known as AR-15512, AVX-012) has been developed as an ophthalmic solution (Tryptyr®) for the treatment of dry eye disease. It received FDA approval in May 2025. It is also used in research on chronic neuropathic pain. The deuterated internal standard is not used in vivo. |
| Enzyme Assay |
General in vitro TRPM8 activation assay (calcium flux): Express human TRPM8 in HEK293 cells. Load cells with Fluo-4 AM (2 uM) for 30 min at 37degC. Add Acoltremon (0.1-1000 nM) and measure fluorescence (ex 488 nm, em 525 nm). Calculate EC₅0 (expected 39 nM). For the deuterated standard, it is not used in this assay. For LC-MS/MS method development, spike a fixed concentration of Acoltremon-d3 (e.g., 10 ng/mL) into calibration standards and unknown samples. Extract samples by protein precipitation or SPE, and analyze by LC-MS/MS (positive ion mode, MRM transitions: parent m/z 334 → 167, internal standard m/z 337 → 170).
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| Cell Assay |
General in vivo protocol for a dry eye model (parent compound): Male NZW rabbits (n=10 per group) are treated with 0.5% Acoltremon ophthalmic solution (one drop) twice daily for 4 weeks. Tear volume is measured by Schirmer test and tear break-up time (TBUT) is measured. Acoltremon significantly increases tear volume and TBUT. For PK, collect plasma at 0, 0.5, 1, 2, 4, 6, 8 h after topical administration for LC-MS analysis. The deuterated standard is used as an internal standard in the PK study.
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| Animal Protocol |
Acoltremon is a small molecule (MW 333.44 for parent). It is administered topically (eye drops) or systemically (i.p. or oral). The deuterated standard has the same ADME properties. Acoltremon is well-absorbed after topical administration to the eye, with low systemic exposure. The plasma half-life is short (t½ ~1-2 h). For research use, Acoltremon-d3 is stored as a solid at -20degC and is soluble in DMSO.
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| ADME/Pharmacokinetics |
The parent compound, Acoltremon, has a good safety profile. In clinical trials, the most common adverse event was mild eye irritation. It is not genotoxic. The deuterated standard is used at trace levels and is safe. For impurity qualification in a drug substance, routine control at 0.15% is acceptable.
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| Toxicity/Toxicokinetics |
Background: Acoltremon (WS-12) is a selective TRPM8 agonist. TRPM8 is a cold-sensitive ion channel that plays a role in tear production and pain sensation. Tryptyr (acoltremon) is the first approved TRPM8 agonist for dry eye disease. The deuterated internal standard is used for accurate quantification in clinical research. It is stored at -20degC and is for research use only.
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| References |
| Molecular Formula |
C18H24D3NO2
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|---|---|
| Molecular Weight |
292.43
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| Related CAS # |
Acoltremon; 68489-09-8
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| Appearance |
White to off-white solid powder
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| Synonyms |
WS-12-d3; AR-15512-d3; AVX-012-d3
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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 : ~16.67 mg/mL (~57.01 mM; with sonication)
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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 | 3.4196 mL | 17.0981 mL | 34.1962 mL | |
| 5 mM | 0.6839 mL | 3.4196 mL | 6.8392 mL | |
| 10 mM | 0.3420 mL | 1.7098 mL | 3.4196 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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