Icilin
Icilin is an agonist at transient receptor potential melastatin 8 (TRPM8) channels; it may block transient receptor potential vanilloid 3 (TRPV3) channels. Icilin displays both hyperalgesic and analgesic activities as well as anti-inflammatory and anticancer properties. Activation of TRPM8 channels induces hyperalgesia and allodynia, but long-term activation desensitizes the channels to induce pain relief. Like menthol, icilin acts as a cooling agent, as TRPM8 channels are cold-sensitive. In animal models of colitis, icilin decreases levels of pro-inflammatory cytokines. Icilin inhibits cell motility in pancreatic ductal adenocarcinoma cells and also decreases levels of E2F1 and induces G1 phase cell cycle arrest in prostate cancer cells.
References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/18931363
| Cas No. |
36945-98-9 |
|---|---|
| Formula |
C16H13N3O4 |
| Formula Wt. |
311.3 |
| IUPAC Name |
3-(2-Hydroxyphenyl)-6-(3-nitrophenyl)-3,4-dihydro-2(1H)-pyrimidinone |
| Synonym |
AG 3-5 |
Burgos-Vega CC, Ahn DD, Bischoff C, et al. Meningeal transient receptor potential channel M8 activation causes cutaneous facial and hindpaw allodynia in a preclinical rodent model of headache. Cephalalgia. 2015 May 5. [Epub ahead of print]. PMID: 25944818.
Hosoya T, Matsumoto K, Tashima K, et al. TRPM8 has a key role in experimental colitis-induced visceral hyperalgesia in mice. Neurogastroenterol Motil. 2014 Aug;26(8):1112-21.PMID: 24832648.
Cucu D, Chiritoiu G, Petrescu S, et al. Characterization of functional transient receptor potential melastatin 8 channels in human pancreatic ductal adenocarcinoma cells. Pancreas. 2014 Jul;43(5):795-800. PMID: 24658318.
Hagenacker T, Lampe M, Schäfers M. Icilin reduces voltage-gated calcium channel currents in naïve and injured DRG neurons in the rat spinal nerve ligation model. Brain Res. 2014 Apr 4;1557:171-9. PMID: 24560602.
Lee S, Chun JN, Kim SH, et al. Icilin inhibits E2F1-mediated cell cycle regulatory programs in prostate cancer. Biochem Biophys Res Commun. 2013 Nov 29;441(4):1005-10. PMID: 24239550.
Ramachandran R, Hyun E, Zhao L, et al. TRPM8 activation attenuates inflammatory responses in mouse models of colitis. Proc Natl Acad Sci U S A. 2013 Apr 30;110(18):7476-81. PMID: 23596210.
Sherkheli MA, Gisselmann G, Hatt H. Supercooling agent icilin blocks a warmth-sensing ion channel TRPV3. ScientificWorldJournal. 2012;2012:982725. PMID: 22548000.
