Target Information
Target General Infomation | |||||
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Target ID |
T41955
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Former ID |
TTDS00507
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Target Name |
TRPM8 protein
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Gene Name |
TRPM8
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Synonyms |
LTrpC6; Long transient receptor potential channel 6; TRPP8; Transient receptor potential-p8; Trp-p8; Transient receptor potential cation channel subfamily M member 8; TRPM8
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Target Type |
Successful
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Disease | Neuropathic pain [ICD9: 356.0, 356.8; ICD10: G64, G90.0] | ||||
Pain [ICD9: 338, 356.0, 356.8,780; ICD10: G64, G90.0, R52, G89] | |||||
Solid tumours [ICD9: 140-199, 210-229; ICD10: C00-D48] | |||||
Throat irritation [ICD9: 478.29; ICD10: J39.2] | |||||
Function |
Receptor-activated non-selective cation channel involved in detection of sensations such as coolness, by being activated by cold temperature below 25 degrees Celsius. Activated by icilin, eucalyptol, menthol, cold and modulation of intracellular pH. Involved in menthol sensation. Permeable for monovalent cations sodium, potassium, and cesium and divalent cation calcium. Temperature sensing is tightly linked to voltage-dependent gating. Activated upon depolarization, changes in temperature resulting in graded shifts of its voltage-dependent activation curves. The chemical agonist menthol functions as a gating modifier, shifting activation curves towards physiological membrane potentials. Temperature sensitivity arises from a tenfold difference in the activation energies associated with voltage-dependent opening and closing. In prostate cancer cells, shows strong inward rectification and high calcium selectivity in contrast to its behavior in normal cells which is characterized by outward rectification and poor cationic selectivity. Plays a role in prostate cancer cell migration (PubMed:25559186). Isoform 2 and isoform 3 negatively regulate menthol- and cold-induced channel activity by stabilizing the closed state of the channel.
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BioChemical Class |
Transient receptor potential catioin channel
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Target Validation |
T41955
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UniProt ID | |||||
Sequence |
MSFRAARLSMRNRRNDTLDSTRTLYSSASRSTDLSYSESDLVNFIQANFKKRECVFFTKD
SKATENVCKCGYAQSQHMEGTQINQSEKWNYKKHTKEFPTDAFGDIQFETLGKKGKYIRL SCDTDAEILYELLTQHWHLKTPNLVISVTGGAKNFALKPRMRKIFSRLIYIAQSKGAWIL TGGTHYGLMKYIGEVVRDNTISRSSEENIVAIGIAAWGMVSNRDTLIRNCDAEGYFLAQY LMDDFTRDPLYILDNNHTHLLLVDNGCHGHPTVEAKLRNQLEKYISERTIQDSNYGGKIP IVCFAQGGGKETLKAINTSIKNKIPCVVVEGSGQIADVIASLVEVEDALTSSAVKEKLVR FLPRTVSRLPEEETESWIKWLKEILECSHLLTVIKMEEAGDEIVSNAISYALYKAFSTSE QDKDNWNGQLKLLLEWNQLDLANDEIFTNDRRWESADLQEVMFTALIKDRPKFVRLFLEN GLNLRKFLTHDVLTELFSNHFSTLVYRNLQIAKNSYNDALLTFVWKLVANFRRGFRKEDR NGRDEMDIELHDVSPITRHPLQALFIWAILQNKKELSKVIWEQTRGCTLAALGASKLLKT LAKVKNDINAAGESEELANEYETRAVELFTECYSSDEDLAEQLLVYSCEAWGGSNCLELA VEATDQHFIAQPGVQNFLSKQWYGEISRDTKNWKIILCLFIIPLVGCGFVSFRKKPVDKH KKLLWYYVAFFTSPFVVFSWNVVFYIAFLLLFAYVLLMDFHSVPHPPELVLYSLVFVLFC DEVRQWYVNGVNYFTDLWNVMDTLGLFYFIAGIVFRLHSSNKSSLYSGRVIFCLDYIIFT LRLIHIFTVSRNLGPKIIMLQRMLIDVFFFLFLFAVWMVAFGVARQGILRQNEQRWRWIF RSVIYEPYLAMFGQVPSDVDGTTYDFAHCTFTGNESKPLCVELDEHNLPRFPEWITIPLV CIYMLSTNILLVNLLVAMFGYTVGTVQENNDQVWKFQRYFLVQEYCSRLNIPFPFIVFAY FYMVVKKCFKCCCKEKNMESSVCCFKNEDNETLAWEGVMKENYLVKINTKANDTSEEMRH RFRQLDTKLNDLKGLLKEIANKIK |
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Drugs and Mode of Action | |||||
Inhibitor | 2-(5-fluoro-1H-indol-3-yl)ethanamine | Drug Info | [531228] | ||
2-(7-(benzyloxy)-1H-indol-3-yl)ethanamine | Drug Info | [531228] | |||
5-Benzyloxytryptamine | Drug Info | [531228] | |||
5-METHOXYTRYPTAMINE | Drug Info | [531228] | |||
PERILLALDEHYDE | Drug Info | [529932] | |||
Blocker (channel blocker) | 2-APB | Drug Info | [531642] | ||
ACAA | Drug Info | [543859] | |||
AMTB | Drug Info | [529542] | |||
M8-B | Drug Info | [531795] | |||
NADA | Drug Info | [543859] | |||
PBMC | Drug Info | [531651] | |||
thio-BCTC | Drug Info | [526953] | |||
Activator | cooling agent 10 | Drug Info | [526953] | ||
CPS125 | Drug Info | [531148] | |||
eucalyptol | Drug Info | [526288] | |||
frescolat MGA | Drug Info | [526953] | |||
frescolat ML | Drug Info | [526953] | |||
geraniol | Drug Info | [526953] | |||
hydroxycitronellal | Drug Info | [526953] | |||
icilin | Drug Info | [530184] | |||
isopulegol | Drug Info | [526953] | |||
linalool | Drug Info | [526953] | |||
Menthol | Drug Info | [537080] | |||
PMD38 | Drug Info | [526953] | |||
WS-12 | Drug Info | [531148] | |||
WS-23 | Drug Info | [526953] | |||
WS-3 | Drug Info | [526953] | |||
WS-5 | Drug Info | [531148] | |||
Modulator | D-3263 | Drug Info | [544089] | ||
PF-05105679 | Drug Info | [532922] | |||
Antagonist | RQ-00203078 | Drug Info | [543859] | ||
Pathways | |||||
KEGG Pathway | Inflammatory mediator regulation of TRP channels | ||||
Reactome | TRP channels | ||||
References | |||||
Ref 522576 | ClinicalTrials.gov (NCT00839631) Dose Escalation Study of EC D-3263 HCl in Advanced Solid Tumors. U.S. National Institutes of Health. | ||||
Ref 532922 | Inhibition of TRPM8 channels reduces pain in the cold pressor test in humans. J Pharmacol Exp Ther. 2014 Nov;351(2):259-69. | ||||
Ref 526288 | Identification of a cold receptor reveals a general role for TRP channels in thermosensation. Nature. 2002 Mar 7;416(6876):52-8. Epub 2002 Feb 10. | ||||
Ref 526953 | 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. Epub 2004Feb 2. | ||||
Ref 529542 | AMTB, a TRPM8 channel blocker: evidence in rats for activity in overactive bladder and painful bladder syndrome. Am J Physiol Renal Physiol. 2008 Sep;295(3):F803-10. | ||||
Ref 529932 | Bioorg Med Chem. 2009 Feb 15;17(4):1636-9. Epub 2008 Dec 30.Taste-guided identification of high potency TRPA1 agonists from Perilla frutescens. | ||||
Ref 530184 | Evolution of thermal response properties in a cold-activated TRP channel. PLoS One. 2009 May 29;4(5):e5741. | ||||
Ref 531148 | Characterization of selective TRPM8 ligands and their structure activity response (S.A.R) relationship. J Pharm Pharm Sci. 2010;13(2):242-53. | ||||
Ref 531228 | Bioorg Med Chem Lett. 2010 Dec 1;20(23):7076-9. Epub 2010 Sep 22.5-benzyloxytryptamine as an antagonist of TRPM8. | ||||
Ref 531642 | 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. | ||||
Ref 531651 | Pharmacological blockade of TRPM8 ion channels alters cold and cold pain responses in mice. PLoS One. 2011;6(9):e25894. | ||||
Ref 531795 | Pharmacological blockade of the cold receptor TRPM8 attenuates autonomic and behavioral cold defenses and decreases deep body temperature. J Neurosci. 2012 Feb 8;32(6):2086-99. | ||||
Ref 532922 | Inhibition of TRPM8 channels reduces pain in the cold pressor test in humans. J Pharmacol Exp Ther. 2014 Nov;351(2):259-69. | ||||
Ref 537080 | TRPV1-mediated itch in seasonal allergic rhinitis. Allergy. 2009 May;64(5):807-10. Epub 2009 Feb 13. |
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