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Chemical compound
Acoltremon Other names AVX-012, WS-12
(1R,2S,5R)-N-(4-methoxyphenyl)-5-methyl-2-propan-2-ylcyclohexane-1-carboxamide
CAS Number PubChem CID DrugBank ChemSpider UNII ChEMBL CompTox Dashboard (EPA ) Formula C 18 H 27 N O 2 Molar mass 289.419 g·mol−1 3D model (JSmol )
C[C@@H]1CC[C@H]([C@@H](C1)C(=O)NC2=CC=C(C=C2)OC)C(C)C
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
Key:HNSGVPAAXJJOPQ-XOKHGSTOSA-N
Acoltremon also known as WS-12 is an investigational new drug which is being evaluated for the treatment of dry eye syndrome .[ 1]
Acoltremon that acts as a potent and selective activator (opener ) of the TRPM8 calcium channel, which is responsible for the sensation of coldness produced by menthol . It is slightly less potent as a TRPM8 activator compared to icilin , but is much more selective for TRPM8 over related calcium channels. It produces analgesic and antiinflammatory effects in animal models with similar efficacy to menthol and a reduced side effect profile.[ 2] [ 3] [ 4] [ 5] [ 6]
^ "Acoltremon - Alcon" . AdisInsight . Springer Nature Switzerland AG.
^ Bödding M, Wissenbach U, Flockerzi V (December 2007). "Characterisation of TRPM8 as a pharmacophore receptor". Cell Calcium . 42 (6): 618–28. doi :10.1016/j.ceca.2007.03.005 . PMID 17517434 .
^ Sherkheli MA, Vogt-Eisele AK, Bura D, Beltrán Márques LR, Gisselmann G, Hatt H (2010). "Characterization of selective TRPM8 ligands and their structure activity response (S.A.R) relationship" . Journal of Pharmacy & Pharmaceutical Sciences . 13 (2): 242–53. doi :10.18433/j3n88n . PMID 20816009 .
^ Liu B, Fan L, Balakrishna S, Sui A, Morris JB, Jordt SE (October 2013). "TRPM8 is the principal mediator of menthol-induced analgesia of acute and inflammatory pain" . Pain . 154 (10): 2169–77. doi :10.1016/j.pain.2013.06.043 . PMC 3778045 . PMID 23820004 .
^ Peixoto-Neves D, Soni H, Adebiyi A (November 2018). "Oxidant-induced increase in norepinephrine secretion from PC12 cells is dependent on TRPM8 channel-mediated intracellular calcium elevation". Biochemical and Biophysical Research Communications . 506 (3): 709–715. doi :10.1016/j.bbrc.2018.10.120 . PMID 30376995 . S2CID 53107273 .
^ Yin Y, Le SC, Hsu AL, Borgnia MJ, Yang H, Lee SY (March 2019). "Structural basis of cooling agent and lipid sensing by the cold-activated TRPM8 channel" . Science . 363 (6430). doi :10.1126/science.aav9334 . PMC 6478609 . PMID 30733385 .
TRPA
Activators
4-Hydroxynonenal
4-Oxo-2-nonenal
4,5-EET
12S-HpETE
15-Deoxy-Δ12,14 -prostaglandin J2
α-Sanshool (ginger , Sichuan and melegueta peppers )
Acrolein
Allicin (garlic )
Allyl isothiocyanate (mustard , radish , horseradish , wasabi )
AM404
ASP-7663
Bradykinin
Cannabichromene (cannabis )
Cannabidiol (cannabis )
Cannabigerol (cannabis )
Cinnamaldehyde (cinnamon )
CR gas (dibenzoxazepine; DBO)
CS gas (2-chlorobenzal malononitrile)
Cuminaldehyde (cumin )
Curcumin (turmeric )
Dehydroligustilide (celery )
Diallyl disulfide
Dicentrine (Lindera spp.)
Farnesyl thiosalicylic acid
Formalin
Gingerols (ginger )
Hepoxilin A3
Hepoxilin B3
Hydrogen peroxide
Icilin
Isothiocyanate
JT-010
Ligustilide (celery , Angelica acutiloba )
Linalool (Sichuan pepper , thyme )
Methylglyoxal
Methyl salicylate (wintergreen )
N-Methylmaleimide
Nicotine (tobacco )
Oleocanthal (olive oil )
Paclitaxel (Pacific yew )
Paracetamol (acetaminophen)
PF-4840154
Phenacyl chloride
Polygodial (Dorrigo pepper )
Shogaols (ginger , Sichuan and melegueta peppers )
Tear gases
Tetrahydrocannabinol (cannabis )
Tetrahydrocannabiorcol
Thiopropanal S-oxide (onion )
Umbellulone (Umbellularia californica )
WIN 55,212-2
Blockers
TRPC
TRPM
TRPML
TRPP
TRPV
Activators
2-APB
5',6'-EET
9-HODE
9-oxoODE
12S-HETE
12S-HpETE
13-HODE
13-oxoODE
20-HETE
α-Sanshool (ginger , Sichuan and melegueta peppers )
Allicin (garlic )
AM404
Anandamide
Bisandrographolide (Andrographis paniculata )
Camphor (camphor laurel , rosemary , camphorweed , African blue basil , camphor basil )
Cannabidiol (cannabis )
Cannabidivarin (cannabis )
Capsaicin (chili pepper )
Carvacrol (oregano , thyme , pepperwort , wild bergamot , others)
DHEA
Diacyl glycerol
Dihydrocapsaicin (chili pepper )
Estradiol
Eugenol (basil , clove )
Evodiamine (Euodia ruticarpa )
Gingerols (ginger )
GSK1016790A
Heat
Hepoxilin A3
Hepoxilin B3
Homocapsaicin (chili pepper )
Homodihydrocapsaicin (chili pepper )
Incensole (incense )
Lysophosphatidic acid
Low pH (acidic conditions)
Menthol (mint )
N-Arachidonoyl dopamine
N-Oleoyldopamine
N-Oleoylethanolamide
Nonivamide (PAVA) (PAVA spray )
Nordihydrocapsaicin (chili pepper )
Paclitaxel (Pacific yew )
Paracetamol (acetaminophen)
Phenylacetylrinvanil
Phorbol esters (e.g., 4α-PDD )
Piperine (black pepper , long pepper )
Polygodial (Dorrigo pepper )
Probenecid
Protons
RhTx
Rutamarin (Ruta graveolens )
Resiniferatoxin (RTX) (Euphorbia resinifera /pooissonii )
Shogaols (ginger , Sichuan and melegueta peppers )
Tetrahydrocannabivarin (cannabis )
Thymol (thyme , oregano )
Tinyatoxin (Euphorbia resinifera /pooissonii )
Tramadol
Vanillin (vanilla )
Zucapsaicin
Blockers