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Details

Stereochemistry ACHIRAL
Molecular Formula C16H13N3O4
Molecular Weight 311.2921
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ICILIN

SMILES

OC1=CC=CC=C1N2CC=C(NC2=O)C3=CC=CC(=C3)[N+]([O-])=O

InChI

InChIKey=RCEFMOGVOYEGJN-UHFFFAOYSA-N
InChI=1S/C16H13N3O4/c20-15-7-2-1-6-14(15)18-9-8-13(17-16(18)21)11-4-3-5-12(10-11)19(22)23/h1-8,10,20H,9H2,(H,17,21)

HIDE SMILES / InChI

Molecular Formula C16H13N3O4
Molecular Weight 311.2921
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/16920620 | https://www.ncbi.nlm.nih.gov/pubmed/11882888 | https://www.ncbi.nlm.nih.gov/pubmed/17353192

AG-3-5 (also known as icilin) was first identified as a super-cooling agent in the early 1980s and bears little resemblance to menthol structurally. Icilin is able to activate both TRPM8 and TRPA1 channel activity. Icilin alleviates pain sensation in animal models.

CNS Activity

Curator's Comment: Icilin is CNS active in animals. No human data available.

Originator

Curator's Comment: refernce retrived from https://www.ncbi.nlm.nih.gov/books/NBK5238/

Approval Year

PubMed

PubMed

TitleDatePubMed
The cold and menthol receptor TRPM8 contains a functionally important double cysteine motif.
2006 Dec 8
Mu and kappa opioid receptor agonists antagonize icilin-induced wet-dog shaking in rats.
2006 Oct 10
Transient receptor potential channel TRPM8 agonists stimulate calcium influx and neurotensin secretion in neuroendocrine tumor cells.
2007
Mice left out in the cold: commentary on the phenotype of TRPM8-nulls.
2007 Aug 17
A pharmacological study of slowly adapting mechanoreceptors responsive to cold thermal stimulation.
2007 Aug 24
Characterisation of TRPM8 as a pharmacophore receptor.
2007 Dec
Differential behavioral effect of the TRPM8/TRPA1 channel agonist icilin (AG-3-5).
2007 Dec 1
Species-specific pharmacology of Trichloro(sulfanyl)ethyl benzamides as transient receptor potential ankyrin 1 (TRPA1) antagonists.
2007 Dec 17
TRPM8-independent menthol-induced Ca2+ release from endoplasmic reticulum and Golgi.
2007 Feb 2
Nalfurafine, the kappa opioid agonist, inhibits icilin-induced wet-dog shakes in rats and antagonizes glutamate release in the dorsal striatum.
2007 Mar
Prospects for prostate cancer imaging and therapy using high-affinity TRPM8 activators.
2007 Mar
TRPM8 is required for cold sensation in mice.
2007 May 3
Transient receptor potential channel A1 is directly gated by calcium ions.
2007 May 4
Plasticity in intact A delta- and C-fibers contributes to cold hypersensitivity in neuropathic rats.
2007 Nov 30
Impairment by activation of TRPA1 of gastric epithelial restitution in a wound model using RGM1 cell monolayer.
2007 Oct
Molecular and cellular limits to somatosensory specificity.
2008 Apr 18
Impairment by allyl isothiocyanate of gastric epithelial wound repair through inhibition of ion transporters.
2008 Dec
Partial restoration of mutant enzyme homeostasis in three distinct lysosomal storage disease cell lines by altering calcium homeostasis.
2008 Feb
Icilin induces a hyperthermia in rats that is dependent on nitric oxide production and NMDA receptor activation.
2008 Jan 14
Plant-derived cannabinoids modulate the activity of transient receptor potential channels of ankyrin type-1 and melastatin type-8.
2008 Jun
Comparison of icilin- and cold-evoked responses of spinal neurones, and their modulation of mechanical activity, in a model of neuropathic pain.
2008 Jun 18
ThermoTRP channels in nociceptors: taking a lead from capsaicin receptor TRPV1.
2008 Mar
HC-030031, a TRPA1 selective antagonist, attenuates inflammatory- and neuropathy-induced mechanical hypersensitivity.
2008 Oct 27
[Modulation of the smooth muscle contractions of the rat vas deferens by TRPM8 channel agonist menthol].
2009
Adult rat odontoblasts lack noxious thermal sensitivity.
2009 Apr
Letter to the editor: "Is menthol- or icilin-induced vasodilation mediated by the activation of TRPM8?".
2009 Aug
Effects of transient receptor potential (TRP) channel agonists and antagonists on slowly adapting type II mechanoreceptors in the rat sinus hair follicle.
2009 Dec
Pore dilation occurs in TRPA1 but not in TRPM8 channels.
2009 Jan 21
Involvement of increased expression of transient receptor potential melastatin 8 in oxaliplatin-induced cold allodynia in mice.
2009 Jul 17
Primary afferents with TRPM8 and TRPA1 profiles target distinct subpopulations of rat superficial dorsal horn neurones.
2009 Jun
Transient receptor potential melastatin 8 channel involvement in the regulation of vascular tone.
2009 Jun
Icilin-induced wet-dog shakes in rats are dependent on NMDA receptor activation and nitric oxide production.
2009 May
Comparative modeling of the quaternary structure for the human TRPM8 channel and analysis of its binding features.
2009 May
Non-neuronal expression of transient receptor potential type A1 (TRPA1) in human skin.
2009 Sep
TRPM8, but not TRPA1, is required for neural and behavioral responses to acute noxious cold temperatures and cold-mimetics in vivo.
2010 Aug
Amiloride-sensitive channels are a major contributor to mechanotransduction in mammalian muscle spindles.
2010 Jan 1
Modulation of the cold-activated cation channel TRPM8 by surface charge screening.
2010 Jan 15
The roles of iPLA2, TRPM8 and TRPA1 in chemically induced cold hypersensitivity.
2010 Jan 21
Intact cutaneous C fibre afferent properties in mechanical and cold neuropathic allodynia.
2010 Jul
Grueneberg ganglion neurons are finely tuned cold sensors.
2010 Jun 2
(-)-Menthylamine derivatives as potent and selective antagonists of transient receptor potential melastatin type-8 (TRPM8) channels.
2010 May 1
Estrogen regulation of TRPM8 expression in breast cancer cells.
2010 May 19
Expression of transient receptor potential channel vanilloid (TRPV) 1–4, melastin (TRPM) 5 and 8, and ankyrin (TRPA1) in the normal and methimazole-treated mouse olfactory epithelium.
2010 Nov
Sensitization of capsaicin and icilin responses in oxaliplatin treated adult rat DRG neurons.
2010 Nov 24
Inhibition of the cardiac L-type calcium channel current by the TRPM8 agonist, (-)-menthol.
2010 Oct
Gating of transient receptor potential melastatin 8 (TRPM8) channels activated by cold and chemical agonists in planar lipid bilayers.
2010 Sep 15
Design and optimization of benzimidazole-containing transient receptor potential melastatin 8 (TRPM8) antagonists.
2011 Jan 13
Transient receptor potential vanilloid-1 (TRPV1) is a mediator of lung toxicity for coal fly ash particulate material.
2012 Mar
TRPM8 activation attenuates inflammatory responses in mouse models of colitis.
2013 Apr 30
Lack of transient receptor potential melastatin 8 activation by phthalate esters that enhance contact hypersensitivity in mice.
2013 Mar 13
Patents

Sample Use Guides

topical application of 80-200 uM icilin alleviates pain sensations in rats
Route of Administration: Topical
Activation of TRPM8 and TRPA1 by Icilin 3-100 uM presynaptically modulated glutamatergic transmission onto partially overlapping but distinct populations of superficial rat dorsal horn neurones.
Substance Class Chemical
Created
by admin
on Thu Jul 06 08:23:46 UTC 2023
Edited
by admin
on Thu Jul 06 08:23:46 UTC 2023
Record UNII
CS70PZQ4QJ
Record Status Validated (UNII)
Record Version
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Name Type Language
ICILIN
MI  
Common Name English
ICILIN [MI]
Common Name English
AG 3-5
Common Name English
1-(2'-HYDROXYPHENYL)-4-(3''-NITROPHENYL)-1,2,3,6-TETRAHYDROPYRIMIDINE-2-ONE
Common Name English
2(1H)-PYRIMIDINONE, 3,6-DIHYDRO-1-(2-HYDROXYPHENYL)-4-(3-NITROPHENYL)-
Systematic Name English
3,6-DIHYDRO-1-(2-HYDROXYPHENYL)-4-(3-NITROPHENYL)-2(1H)-PYRIMIDINONE
Systematic Name English
Code System Code Type Description
MESH
C490483
Created by admin on Thu Jul 06 08:23:46 UTC 2023 , Edited by admin on Thu Jul 06 08:23:46 UTC 2023
PRIMARY
MERCK INDEX
M6195
Created by admin on Thu Jul 06 08:23:46 UTC 2023 , Edited by admin on Thu Jul 06 08:23:46 UTC 2023
PRIMARY Merck Index
EPA CompTox
DTXSID70190442
Created by admin on Thu Jul 06 08:23:46 UTC 2023 , Edited by admin on Thu Jul 06 08:23:46 UTC 2023
PRIMARY
FDA UNII
CS70PZQ4QJ
Created by admin on Thu Jul 06 08:23:46 UTC 2023 , Edited by admin on Thu Jul 06 08:23:46 UTC 2023
PRIMARY
WIKIPEDIA
ICILIN
Created by admin on Thu Jul 06 08:23:46 UTC 2023 , Edited by admin on Thu Jul 06 08:23:46 UTC 2023
PRIMARY
PUBCHEM
161930
Created by admin on Thu Jul 06 08:23:46 UTC 2023 , Edited by admin on Thu Jul 06 08:23:46 UTC 2023
PRIMARY
CAS
36945-98-9
Created by admin on Thu Jul 06 08:23:46 UTC 2023 , Edited by admin on Thu Jul 06 08:23:46 UTC 2023
PRIMARY