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
Nociceptor and hair cell transducer properties of TRPA1, a channel for pain and hearing.	2005 Apr 20	15843607
Novel role of cold/menthol-sensitive transient receptor potential melastatine family member 8 (TRPM8) in the activation of store-operated channels in LNCaP human prostate cancer epithelial cells.	2005 Nov 25	16174775
Analgesia mediated by the TRPM8 cold receptor in chronic neuropathic pain.	2006 Aug 22	16920620
The cold and menthol receptor TRPM8 contains a functionally important double cysteine motif.	2006 Dec 8	17015441
Cool and menthol receptor TRPM8 in human urinary bladder disorders and clinical correlations.	2006 Mar 6	16519806
Transient receptor potential channel TRPM8 agonists stimulate calcium influx and neurotensin secretion in neuroendocrine tumor cells.	2007	17426390
Mice left out in the cold: commentary on the phenotype of TRPM8-nulls.	2007 Aug 17	17705869
Differential behavioral effect of the TRPM8/TRPA1 channel agonist icilin (AG-3-5).	2007 Dec 1	17765220
Species-specific pharmacology of Trichloro(sulfanyl)ethyl benzamides as transient receptor potential ankyrin 1 (TRPA1) antagonists.	2007 Dec 17	18086308
Contractile effect of TRPA1 receptor agonists in the isolated mouse intestine.	2007 Dec 8	17825279
Plasticity in intact A delta- and C-fibers contributes to cold hypersensitivity in neuropathic rats.	2007 Nov 30	17945425
Plant-derived cannabinoids modulate the activity of transient receptor potential channels of ankyrin type-1 and melastatin type-8.	2008 Jun	18354058
HC-030031, a TRPA1 selective antagonist, attenuates inflammatory- and neuropathy-induced mechanical hypersensitivity.	2008 Oct 27	18954467
Inorganic polyphosphate modulates TRPM8 channels.	2009	19404398
Tumor necrosis factor-alpha (TNF-alpha) enhances functional thermal and chemical responses of TRP cation channels in human synoviocytes.	2009 Aug 20	19695100
Effects of transient receptor potential (TRP) channel agonists and antagonists on slowly adapting type II mechanoreceptors in the rat sinus hair follicle.	2009 Dec	20021572
Primary afferents with TRPM8 and TRPA1 profiles target distinct subpopulations of rat superficial dorsal horn neurones.	2009 Jun	19371346
Evolution of thermal response properties in a cold-activated TRP channel.	2009 May 29	19492038
Non-neuronal expression of transient receptor potential type A1 (TRPA1) in human skin.	2009 Sep	19282836
Characterization of selective TRPM8 ligands and their structure activity response (S.A.R) relationship.	2010	20816009
The roles of iPLA2, TRPM8 and TRPA1 in chemically induced cold hypersensitivity.	2010 Jan 21	20092626
Inhibition of the cardiac L-type calcium channel current by the TRPM8 agonist, (-)-menthol.	2010 Oct	21081797
Dissociation of μ- and δ-opioid inhibition of glutamatergic synaptic transmission in superficial dorsal horn.	2010 Oct 26	20977770

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