ICILIN

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 Search

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
Sources: https://www.ncbi.nlm.nih.gov/books/NBK5238/
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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Transient receptor potential cation channel subfamily M member 8 18 Target ID: CHEMBL1075319 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19230823 \| https://www.ncbi.nlm.nih.gov/pubmed/15363396 \| https://www.ncbi.nlm.nih.gov/pubmed/11882888	Agonist 2678
Transient receptor potential cation channel subfamily A member 1 38 Target ID: CHEMBL6007 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17353192	Agonist 2678

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain 614 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16920620	Primary		Basic research	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
A TRP channel that senses cold stimuli and menthol.	2002 Mar 8	11893340
Thermosensitive transient receptor potential channels in vagal afferent neurons of the mouse.	2004 Jun	14726308
Two populations of cold-sensitive neurons in rat dorsal root ganglia and their modulation by nerve growth factor.	2004 Nov	15525269
How cold is it? TRPM8 and TRPA1 in the molecular logic of cold sensation.	2005 Apr 22	15847696
EGF suppresses hydrogen peroxide induced Ca2+ influx by inhibiting L-type channel activity in cultured human corneal endothelial cells.	2005 Feb	15670807
Functional expression of thermo-transient receptor potential channels in dental primary afferent neurons: implication for tooth pain.	2006 Jun 23	16595689
Icilin evokes a dose- and time-dependent increase in glutamate within the dorsal striatum of rats.	2006 May	16622598
Species-specific pharmacology of Trichloro(sulfanyl)ethyl benzamides as transient receptor potential ankyrin 1 (TRPA1) antagonists.	2007 Dec 17	18086308
TRPM8-independent menthol-induced Ca2+ release from endoplasmic reticulum and Golgi.	2007 Feb 2	17142461
Regulation of transient receptor potential channels of melastatin type 8 (TRPM8): effect of cAMP, cannabinoid CB(1) receptors and endovanilloids.	2007 May 15	17428469
Attenuated cold sensitivity in TRPM8 null mice.	2007 May 3	17481392
Plasticity in intact A delta- and C-fibers contributes to cold hypersensitivity in neuropathic rats.	2007 Nov 30	17945425
Impairment by activation of TRPA1 of gastric epithelial restitution in a wound model using RGM1 cell monolayer.	2007 Oct	17943255
Partial restoration of mutant enzyme homeostasis in three distinct lysosomal storage disease cell lines by altering calcium homeostasis.	2008 Feb	18254660
Icilin induces a hyperthermia in rats that is dependent on nitric oxide production and NMDA receptor activation.	2008 Jan 14	17976579
ThermoTRP channels in nociceptors: taking a lead from capsaicin receptor TRPV1.	2008 Mar	19305786
Adult rat odontoblasts lack noxious thermal sensitivity.	2009 Apr	19407152
Letter to the editor: "Is menthol- or icilin-induced vasodilation mediated by the activation of TRPM8?".	2009 Aug	19635848
Involvement of increased expression of transient receptor potential melastatin 8 in oxaliplatin-induced cold allodynia in mice.	2009 Jul 17	19375484
Transient receptor potential melastatin 8 channel involvement in the regulation of vascular tone.	2009 Jun	19363131
Chronic treatment with NGF induces spontaneous fluctuations of intracellular Ca(2+) in icilin-sensitive dorsal root ganglion neurons of the rat.	2010 Dec	20657161
Modulation of the cold-activated cation channel TRPM8 by surface charge screening.	2010 Jan 15	19948654
Design and optimization of benzimidazole-containing transient receptor potential melastatin 8 (TRPM8) antagonists.	2011 Jan 13	21128593
Transient receptor potential vanilloid-1 (TRPV1) is a mediator of lung toxicity for coal fly ash particulate material.	2012 Mar	22155782

Patents

Sample Use Guides

In Vivo Use Guide

topical application of 80-200 uM icilin alleviates pain sensations in rats

Route of Administration: Topical

In Vitro Use Guide

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 `Sat Dec 16 02:08:39 GMT 2023` Edited by `admin` on `Sat Dec 16 02:08:39 GMT 2023`
Record UNII	CS70PZQ4QJ
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ICILIN

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