Description
Icilin (36945-98-9) is an activator of cold-sensitive TRP channels with 2.5-fold greater efficacy and 200-fold greater potency than menthol (EC50= 0.36 μM for CRM1, rat orthologue of TRPM8).1 Activator at TRPM8 (EC50= 0.2 μM)2and ANKTM1(TRPA1)3. Activator effects require Ca2+and are pH dependent.2,4Icilin induced G1arrest in PC-3 prostate cancer cells without cell death.5
General Description
Icilin is a synthetic cooling agent and modulates human transient receptor potential cation channel (TRPA1). Icilin inhibits transient receptor potential cation channel subfamily M member 8 (TRPM8) and modulates calcium release. Icilin also suppresses transient receptor potential vanilloid subtype 3 (TRPV3).
Biological Activity
Cooling agent that activates the novel cold receptors TRPM8 (CMR1) and TRPA1 (ANKTM1/TRPN1), members of the TRP ion channel family. Induces currents in CMR1-expressing HEK-293 cells (EC 50 = 0.36 μ M) more potently than menthol or low temperatures. Produces "wet shakes" in vivo .
References
[1] DAVID D. MCKEMY David J Werner M Neuhausser. Identification of a cold receptor reveals a general role for TRP channels in thermosensation[J]. Nature, 2002, 416 6876: 52-58. DOI:
10.1038/nature719[2] DAVID A ANDERSSON Stuart B Henry W N Chase. TRPM8 activation by menthol, icilin, and cold is differentially modulated by intracellular pH.[J]. Journal of Neuroscience, 2004, 24 23: 5364-5369. DOI:
10.1523/jneurosci.0890-04.2004[3] GINA M STORY. ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures.[J]. Cell, 2003, 112 6: 819-829. DOI:
10.1016/s0092-8674(03)00158-2[4] HUAI-HU CHUANG David J Werner M Neuhausser. The super-cooling agent icilin reveals a mechanism of coincidence detection by a temperature-sensitive TRP channel.[J]. Neuron, 2004, 43 6: 859-869. DOI:
10.1016/j.neuron.2004.08.038[5] SU-HWA KIM . Icilin induces G1 arrest through activating JNK and p38 kinase in a TRPM8-independent manner[J]. Biochemical and biophysical research communications, 2011, 406 1: Pages 30-35. DOI:
10.1016/j.bbrc.2011.01.094
