Acoltremon

Acoltremon
Clinical data
Other names	AVX-012, WS-12
Identifiers
	IUPAC name (1R,2S,5R)-N-(4-methoxyphenyl)-5-methyl-2-propan-2-ylcyclohexane-1-carboxamide;
CAS Number	68489-09-8;
PubChem CID	11266244;
DrugBank	DB19202;
ChemSpider	9441255;
UNII	1L7BVT4Z4Z;
ChEMBL	ChEMBL2441929;
CompTox Dashboard (EPA)	DTXSID10460636 ;
Chemical and physical data
Formula	C18H27NO2
Molar mass	289.419 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C[C@@H]1CC[C@H]([C@@H](C1)C(=O)NC2=CC=C(C=C2)OC)C(C)C;
	InChI 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]

References

^ "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.

[1] "Acoltremon - Alcon". AdisInsight. Springer Nature Switzerland AG.

[2] 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.

[3] 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.

[4] 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.

[5] 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.

[6] 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.

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References

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