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acoltremon   Click here for help

GtoPdb Ligand ID: 4343

Synonyms: AR-15512 | AR15512 | AVX-012 | Tryptyr® | WS 12 | WS-12
Approved drug PDB Ligand
acoltremon is an approved drug
Compound class: Synthetic organic
Comment: Acoltremon (AR-15512) is a transient receptor potential melastatin 8 (TRPM8) agonist [1-3]. Topical application of TRPM8 agonists was proposed to relieve ocular pain and discomfort in dry eye disease [5-6], via stimulation of tear production through opening of TRPM8 calcium channels expressed in branches of the trigeminal nerve that innervate the cornea and eye lids. It also produces menthol-like cooling effects.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species

acoltremon is commercially available from our sponsors

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 2
Hydrogen bond donors 1
Rotatable bonds 5
Topological polar surface area 38.33
Molecular weight 289.2
XLogP 5.2
No. Lipinski's rules broken 1

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES COc1ccc(cc1)NC(=O)C1CC(C)CCC1C(C)C
Isomeric SMILES COc1ccc(cc1)NC(=O)[C@@H]1C[C@H](C)CC[C@H]1C(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
InChI Key HNSGVPAAXJJOPQ-XOKHGSTOSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
1. Ma S, G G, Ak VE, Jf D, H H. (2008)
Menthol derivative WS-12 selectively activates transient receptor potential melastatin-8 (TRPM8) ion channels.
Pak J Pharm Sci, 21 (4): 370-8. [PMID:18930858]
2. Rodríguez-Arévalo S, Pujol E, Abás S, Galdeano C, Escolano C, Vázquez S. (2021)
Synthesis, Characterization and HPLC Analysis of the (1S,2S,5R)-Diastereomer and the Enantiomer of the Clinical Candidate AR-15512.
Molecules, 26 (4). [PMID:33572112]
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.
J Pharm Pharm Sci, 13 (2): 242-53. [PMID:20816009]
4. Wirta DL, Senchyna M, Lewis AE, Evans DG, McLaurin EB, Ousler GW, Hollander DA. (2022)
A randomized, vehicle-controlled, Phase 2b study of two concentrations of the TRPM8 receptor agonist AR-15512 in the treatment of dry eye disease (COMET-1).
Ocul Surf, 26: 166-173. [PMID:35970431]
5. Yang JM, Li F, Liu Q, Rüedi M, Wei ET, Lentsman M, Lee HS, Choi W, Kim SJ, Yoon KC. (2017)
A novel TRPM8 agonist relieves dry eye discomfort.
BMC Ophthalmol, 17 (1): 101. [PMID:28651550]
6. Yoon HJ, Kim J, Yang JM, Wei ET, Kim SJ, Yoon KC. (2021)
Topical TRPM8 Agonist for Relieving Neuropathic Ocular Pain in Patients with Dry Eye: A Pilot Study.
J Clin Med, 10 (2). [PMID:33445485]