| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 100mg | |||
| 250mg | |||
| Other Sizes |
| Targets |
TRPM8
WS-12 targets the transient receptor potential melastatin 8 (TRPM8) ion channel. TRPM8 is a non-selective cation channel that is activated by cold temperatures and cooling agents such as menthol and icilin. By acting as an agonist, WS-12 activates TRPM8, leading to an influx of calcium ions and the generation of action potentials in sensory neurons. This activation produces a cooling sensation and can modulate pain signaling. |
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| ln Vitro |
In tests involving heterologously produced TRP ion channels, Acoltremon (10 μM) exhibits TRPM8 agonism [1]. In DRG neurons, acoltremon (1 or 10 μM; 0-250 s) seems to be a very strong and selective TRPM8 channel agonist [1].
WS-12 is a potent TRPM8 agonist with an EC50 of 39 nM. It displays higher potency and efficacy compared to menthol (EC50 = 193 μM). At concentrations up to 1 mM, it does not activate other thermo-sensitive TRP channels including TRPV1, TRPV2, TRPV3, TRPV4, and TRPA1, indicating its selectivity for TRPM8. |
| ln Vivo |
In mice, acoltremon (ip; 10 mg/kg; once) produces analgesic effects by activating TRPM8 specifically [1].
WS-12 has shown analgesic effects in preclinical models and can be used in chronic neuropathic pain research. It is a potentially first-in-class compound for the treatment of dry eye and chronic neuropathic pain. Its high potency and selectivity for TRPM8 make it a valuable tool for studying the role of this channel in pain and other physiological processes. |
| Enzyme Assay |
The in vitro assay for WS-12 typically involves measuring its activity at the TRPM8 channel using calcium imaging or electrophysiology. Cells expressing TRPM8 are treated with varying concentrations of the compound, and the influx of calcium is measured using a fluorescent calcium indicator. The EC50 value is determined from the dose-response curve.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: HEK293T Cell Tested Concentrations: 10 μM Incubation Duration: Experimental Results: Activates mouse TRPM8 (mTRPM8), but neither activates nor inhibits mTRPA1. Cell viability assay[1] Cell Types: Cultured Mouse DRG Neurons Tested Concentrations: 1 or 10 μM Incubation Duration: 0-250 s Experimental Results: Approximately 10% to 14% of cultured wild-type neurons were shown to respond to WS-12 . The in vitro cellular assay for WS-12 typically involves culturing cells that express TRPM8, such as dorsal root ganglion neurons or transfected cell lines. Cells are treated with varying concentrations of the compound, and intracellular calcium levels are measured using fluorescence microscopy or a plate reader. The compound's ability to activate TRPM8 and induce calcium influx is quantified. |
| Animal Protocol |
Animal/Disease Models: Trpm8–/– mice and capsaicin-injected mice [1]
Doses: 10 mg/kg Route of Administration: intraperitoneal (ip) injection; 10 mg/kg; primary Experimental Results:significant analgesic effect in Trpm8-/ -The effect is lost in mice. In the rotarod test, mice demonstrated no change in latency decline. Reducing capsaicin-induced nociceptive behavior. In vivo animal studies for WS-12 would typically involve the use of rodent models of pain or dry eye. The compound would be administered via topical, intraperitoneal, or oral routes. Pain responses would be assessed using standard pain tests, and dry eye symptoms would be evaluated by measuring tear production and corneal staining. |
| ADME/Pharmacokinetics |
WS-12 has a molecular weight of 289.41 g/mol and a molecular formula of C18H27NO2. The IUPAC name is (1R,2R,5S)-N-(4-methoxyphenyl)-2,5-dimethylbicyclo[3.1.0]hexane-2-carboxamide. The compound has a purity of 99.99%. It is also known as AVX-012, AR-15512, and Acoltremon. Further detailed PK parameters are not available in the public domain.
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| Toxicity/Toxicokinetics |
(1R,2S,5R)-N-(4-methoxyphenyl)-5-methyl-2-(1-methylethyl)-cyclohexaneformamide 2147 Scientific opinion on Fragrance Group Assessment 304 (FGE.304): From the Committee Regulation (EC) No 1565/2000 on Five Formamides in Group 30 of Chemistry (repealed by Committee Implementing Regulation (EU) No 872/2012) doi:10.2903/j.efsa.2012.2903 2012-10-12
(1R,2S,5R)-N-(4-methoxyphenyl)-5-methyl-2-(1-methylethyl)-cyclohexaneformamide 2524 Scientific opinion on Fragrance Group Assessment 304, Revision 1 (FGE.304Rev1): From Group 30 of Chemistry Four types of formamide were listed in Commission Regulation (EC) 1565/2000 (which was repealed by European Commission Implementing Regulation 872/2012) doi:10.2903/j.efsa.2014.3769 2014-07-22 Specific toxicology data for WS-12 are not available in the public domain. The compound is intended for research use only and should be handled with appropriate laboratory safety precautions. Standard safety assessments would be required before any clinical application. Researchers should consult the safety data sheet for detailed handling and disposal information. |
| References | |
| Additional Infomation |
Acoltremon is being investigated in the clinical trial NCT05493111 (a long-term safety study evaluating the safety and systemic exposure of AR-15512). In the pivotal Phase 3 trial, TRYPTYR showed rapid promotion of natural tear production as early as day 1. TRYPTYR is a first-in-class TRPM8 receptor agonist that rapidly stimulates natural tear production in patients with dry eye syndrome (DED). Approximately 38 million people in the United States suffer from dry eye syndrome, but less than 10% of diagnosed patients receive prescription treatment.
Acoltremon is also known as WS-12, AR-15512, AVX-012, and has the brand name Tryptyr. It is a potent and selective agonist of the TRPM8 ion channel. It is a synthetic carboxamide derivative of menthol and acts as a cooling agent. It has an EC50 of 39 nM, making it approximately 2000-fold more potent than menthol. It is being developed for the treatment of dry eye and chronic neuropathic pain. It has not yet entered clinical trials and is strictly for preclinical research purposes. |
| Molecular Formula |
C18H27NO2
|
|---|---|
| Molecular Weight |
289.419
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| Exact Mass |
289.204
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| Elemental Analysis |
C, 74.70; H, 9.40; N, 4.84; O, 11.06
|
| CAS # |
68489-09-8
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| PubChem CID |
11266244
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| Appearance |
White to off-white solid powder
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| LogP |
4.415
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| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
21
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| Complexity |
334
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| Defined Atom Stereocenter Count |
3
|
| SMILES |
C[C@@H]1CC[C@H]([C@@H](C1)C(=O)NC2=CC=C(C=C2)OC)C(C)C
|
| InChi Key |
HNSGVPAAXJJOPQ-XOKHGSTOSA-N
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| InChi Code |
InChI=1S/C18H27NO2/c1-12(2)16-10-5-13(3)11-17(16)18(20)19-14-6-8-15(21-4)9-7-14/h6-9,12-13,16-17H,5,10-11H2,1-4H3,(H,19,20)/t13-,16+,17-/m1/s1
|
| Chemical Name |
(1R,2S,5R)-N-(4-methoxyphenyl)-5-methyl-2-propan-2-ylcyclohexane-1-carboxamide
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| Synonyms |
WS12; WS-12; (1R,2S,5R)-N-(4-methoxyphenyl)-5-methyl-2-(propan-2-yl)cyclohexane-1-carboxamide; Fema No. 4681; ...; Acoltremon; WS 12
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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 : ~20 mg/mL (~69.11 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2 mg/mL (6.91 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.4552 mL | 17.2759 mL | 34.5519 mL | |
| 5 mM | 0.6910 mL | 3.4552 mL | 6.9104 mL | |
| 10 mM | 0.3455 mL | 1.7276 mL | 3.4552 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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