Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMYVOL9)

• Drug Name: icilin Drug Info
• Synonyms: Icilin; 36945-98-9; AG 3-5; 3-(2-hydroxyphenyl)-6-(3-nitrophenyl)-3,4-dihydropyrimidin-2(1H)-one; Icilin(AG 3-5); UNII-CS70PZQ4QJ; ICILLIN; 2(1H)-Pyrimidinone, 3,6-dihydro-1-(2-hydroxyphenyl)-4-(3-nitrophenyl)-; CS70PZQ4QJ; BRN 0700310; CHEMBL258405; 3,6-Dihydro-1-(2-hydroxyphenyl)-4-(3-nitrophenyl)-2(1H)-pyrimidinone; AG-3-5; 1-(2-Hydroxyphenyl)-4-(3-nitrophenyl)-1,2,3,6-tetrahydropyrimidine-2-one; 2(1H)-Pyrimidinone,3,6-dihydro-1-(2-hydroxyphenyl)-4-(3-nitrophenyl)-

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 161930
  ChEBI ID: CHEBI:92845
  CAS Number: CAS 36945-98-9
  TTD Drug ID: DMYVOL9

Molecule-Related Drug Atlas

Drug(s) Targeting Long transient receptor potential channel 8 (TRPM8)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Menthol	DMG2KW7	Back pain	ME84.Z	Approved	[5]
D-3263	DM7V2OM	Solid tumour/cancer	2A00-2F9Z	Phase 1	[6]
PF-05105679	DM4QPT0	Pain	MG30-MG3Z	Phase 1	[7]
2-APB	DM9AKVR	Discovery agent	N.A.	Investigative	[8]
ACAA	DMACYPW	Discovery agent	N.A.	Investigative	[9]
5-METHOXYTRYPTAMINE	DMARCKD	Discovery agent	N.A.	Investigative	[10]
2-(5-fluoro-1H-indol-3-yl)ethanamine	DMHW5FT	Discovery agent	N.A.	Investigative	[10]
NADA	DM3ORGM	Discovery agent	N.A.	Investigative	[9]
2-(7-(benzyloxy)-1H-indol-3-yl)ethanamine	DMD2QVO	Discovery agent	N.A.	Investigative	[10]
linalool	DMGZQ5P	Discovery agent	N.A.	Investigative	[11]

Drug(s) Targeting Transformation-sensitive protein p120 (TRPA1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Menthol	DMG2KW7	Back pain	ME84.Z	Approved	[5]
LY3526318	DMFXNQM	Chronic low-back pain	MG30	Phase 2	[12]
HX-100	DMFRM15	Diabetic neuropathy	8C0Z	Phase 1	[13]
NPPB	DMFIWAN	Discovery agent	N.A.	Investigative	[14]
acetaldehyde	DMJFKG4	Discovery agent	N.A.	Investigative	[15]
[3H]resolvin D1	DMFT0HU	Discovery agent	N.A.	Investigative	[16]
Formaldehyde	DM7Q6M0	Discovery agent	N.A.	Investigative	[17]
4-oxo-nonenal	DMPX1J9	Discovery agent	N.A.	Investigative	[18]
dibutyl phthalate	DMEDGKO	Discovery agent	N.A.	Investigative	[19]
prostaglandin A2	DMWC4X8	Discovery agent	N.A.	Investigative	[20]

Drug(s) Affected By Cyclin-dependent kinase inhibitor 1 (CDKN1A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[21]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[22]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[23]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[24]
Talazoparib	DM1KS78	Breast cancer	2C60-2C65	Approved	[25]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[26]
Etretinate	DM2CZFA	Keratosis	ED56	Approved	[27]
Prednisone	DM2HG4X	Acute asthma	CA23	Approved	[28]
Ciprofloxacin XR	DM2NLS9	Acute gonococcal cervicitis		Approved	[29]
Colchicine	DM2POTE	Acute gout flare	FA25.0	Approved	[30]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Long transient receptor potential channel 8 (TRPM8)	TTXDKTO	TRPM8_HUMAN	Activator	[2]
Transformation-sensitive protein p120 (TRPA1)	TTELV3W	TRPA1_HUMAN	Activator	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Gene/Protein Processing	[4]

References

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• [2] Evolution of thermal response properties in a cold-activated TRP channel. PLoS One. 2009 May 29;4(5):e5741.
• [3] ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures. Cell. 2003 Mar 21;112(6):819-29.
• [4] Transient Receptor Potential Melastatin 8, a sensor of cold temperatures mediates expression of cyclin-dependent kinase inhibitor, p21/Cip1, a regulator of epidermal cell proliferation. J Toxicol Sci. 2022;47(3):117-123. doi: 10.2131/jts.47.117.
• [5] TRPV1-mediated itch in seasonal allergic rhinitis. Allergy. 2009 May;64(5):807-10.
• [6] Best of the 2009 AUA Annual Meeting: Highlights from the 2009 Annual Meeting of the American Urological Association, April 25-30, 2009, Chicago, IL. Rev Urol. 2009 Spring; 11(2): 82-107.
• [7] Inhibition of TRPM8 channels reduces pain in the cold pressor test in humans. J Pharmacol Exp Ther. 2014 Nov;351(2):259-69.
• [8] Effects of antagonists and heat on TRPM8 channel currents in dorsal root ganglion neuron activated by nociceptive cold stress and menthol. Neurochem Res. 2012 Feb;37(2):314-20.
• [9] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 500).
• [10] 5-benzyloxytryptamine as an antagonist of TRPM8. Bioorg Med Chem Lett. 2010 Dec 1;20(23):7076-9.
• [11] Characterization of the mouse cold-menthol receptor TRPM8 and vanilloid receptor type-1 VR1 using a fluorometric imaging plate reader (FLIPR) assay. Br J Pharmacol. 2004 Feb;141(4):737-45.
• [12] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2023. Adis Insight
• [13] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [14] NPPB structure-specifically activates TRPA1 channels. Biochem Pharmacol. 2010 Jul 1;80(1):113-21.
• [15] Transient receptor potential A1 mediates acetaldehyde-evoked pain sensation. Eur J Neurosci. 2007 Nov;26(9):2516-23.
• [16] Resolvin D1 attenuates activation of sensory transient receptor potential channels leading to multiple anti-nociception. Br J Pharmacol. 2010 Oct;161(3):707-20.
• [17] An ion channel essential for sensing chemical damage. J Neurosci. 2007 Oct 17;27(42):11412-5.
• [18] Transient receptor potential A1 is a sensory receptor for multiple products of oxidative stress. J Neurosci. 2008 Mar 5;28(10):2485-94.
• [19] TRPA1 and TRPV1 activation is a novel adjuvant effect mechanism in contact hypersensitivity. J Neuroimmunol. 2009 Feb 15;207(1-2):66-74.
• [20] Cox-dependent fatty acid metabolites cause pain through activation of the irritant receptor TRPA1. Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):12045-50.
• [21] Zidovudine induces S-phase arrest and cell cycle gene expression changes in human cells. Mutagenesis. 2005 Mar;20(2):139-46. doi: 10.1093/mutage/gei019. Epub 2005 Mar 22.
• [22] Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J Cell Biochem. 2017 Jun;118(6):1531-1546. doi: 10.1002/jcb.25815. Epub 2016 Dec 29.
• [23] Gene expression profiles with activation of the estrogen receptor alpha-selective estrogen receptor modulator complex in breast cancer cells expressing wild-type estrogen receptor. Cancer Res. 2002 Aug 1;62(15):4419-26.
• [24] Leptomycin B reduces primary and acquired resistance of gefitinib in lung cancer cells. Toxicol Appl Pharmacol. 2017 Nov 15;335:16-27. doi: 10.1016/j.taap.2017.09.017. Epub 2017 Sep 21.
• [25] BMN 673 (talazoparib): A potent PARP inhibitor for triple negative breast cancer with different genetic profile. J Biochem Mol Toxicol. 2019 May;33(5):e22286. doi: 10.1002/jbt.22286. Epub 2019 Jan 23.
• [26] Gene expression after treatment with hydrogen peroxide, menadione, or t-butyl hydroperoxide in breast cancer cells. Cancer Res. 2002 Nov 1;62(21):6246-54.
• [27] Bexarotene activates the p53/p73 pathway in human cutaneous T-cell lymphoma. Br J Dermatol. 2009 Mar;160(3):519-26. doi: 10.1111/j.1365-2133.2008.08931.x. Epub 2008 Nov 25.
• [28] Glucocorticoids induce G1 arrest of lymphoblastic cells through retinoblastoma protein Rb1 dephosphorylation in childhood acute lymphoblastic leukemia in vivo. Cancer Biol Ther. 2004 May;3(5):470-6. doi: 10.4161/cbt.3.5.838. Epub 2004 May 9.
• [29] Ciprofloxacin mediated cell growth inhibition, S/G2-M cell cycle arrest, and apoptosis in a human transitional cell carcinoma of the bladder cell line. Clin Cancer Res. 2000 Mar;6(3):891-900.
• [30] Utilization of CDKN1A/p21 gene for class discrimination of DNA damage-induced clastogenicity. Toxicology. 2014 Jan 6;315:8-16. doi: 10.1016/j.tox.2013.10.009. Epub 2013 Nov 6.