Target Validation Information
Target ID T83193
Target Name Vanilloid receptor 1
Target Type
Successful
Drug Potency against Target A-425619 Drug Info IC50 = 4 nM [552879]
IODORESINIFERATOXIN Drug Info Ki = 12.2 nM [529209]
(E)-3-(4-tert-Butyl-phenyl)-N-phenyl-acrylamide Drug Info IC50 = 330 nM [527363]
Pyrrolidin-1-yl-thiourea Drug Info IC50 = 3000 nM [527001]
1-benzhydryl-3-(isoquinolin-5-yl)urea Drug Info IC50 = 600 nM [528843]
4-(methyl(nonyl)amino)-N-(quinolin-3-yl)benzamide Drug Info IC50 = 150 nM [529389]
4-(hexyl(methyl)amino)-N-(quinolin-3-yl)benzamide Drug Info IC50 = 86 nM [529389]
SC-0030 Drug Info IC50 = 40 nM [530533]
4-pentyl-N-pyridin-3-yl benzamide Drug Info Ki = 421 nM [529389]
ABT-102 Drug Info IC50 = 4 nM [552879]
AMG-628 Drug Info IC50 = 2 nM [528915]
1-(4-Bromo-benzyl)-3-quinazolin-8-yl-urea Drug Info IC50 = 170 nM [527423]
(5E,8E,11E,14E)-Icosa-5,8,11,14-tetraenal Drug Info IC50 = 51 nM [527623]
1-(isoquinolin-5-yl)-3-(4-morpholinobenzyl)urea Drug Info IC50 = 91 nM [528909]
N-(4-tert-butylphenyl)-4-(pyridin-2-yl)benzamide Drug Info IC50 = 8 nM [528334]
(E)-Octadec-9-enal Drug Info IC50 = 35 nM [527623]
ATC-120 Drug Info IC50 = 50 nM [530533]
MK-056 Drug Info IC50 = 110 nM [530533]
CAPSAZEPINE Drug Info IC50 = 887 nM [528825]
4-Pyridin-2-yl-piperazine-1-carboxylic acid amide Drug Info IC50 = 30 nM [527001]
6'-Iodononivamide Drug Info Ki = 127 nM [531210]
4-(3-methylpyridin-2-yl)-N-p-tolylbenzamide Drug Info IC50 = 2585 nM [528334]
1,3-dibenzyl urea Drug Info IC50 = 10 nM [529279]
(S)-1-(1H-indazol-4-yl)-3-(1-p-tolylethyl)urea Drug Info IC50 = 749 nM [528843]
1-(isoquinolin-5-yl)-3-(1-phenylpropyl)urea Drug Info IC50 = 2580 nM [528843]
BCTC Drug Info IC50 = 7 nM [552879]
AMG-517 Drug Info IC50 = 0.8 nM [552895]
N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]lauramide Drug Info IC50 = 740 nM [529162]
N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]linoleamide Drug Info IC50 = 1820 nM [529162]
N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]undecanamide Drug Info IC50 = 760 nM [529162]
A-795614 Drug Info IC50 = 30 nM [529652]
JNJ-17203212 Drug Info IC50 = 16 nM [528825]
N-(4-iodophenyl)-4-(trifluoromethoxy)benzamide Drug Info IC50 = 280 nM [529233]
N-(4-iodophenyl)-4-(trifluoromethyl)benzamide Drug Info IC50 = 330 nM [529233]
4-butyl-N-(pyridin-3-yl)benzamide Drug Info Ki = 626 nM [529389]
4-propyl-N-(quinolin-3-yl)benzamide Drug Info IC50 = 130 nM [529389]
4-octyl-N-(pyridin-3-yl)benzamide Drug Info Ki = 546 nM [529389]
2-(4-pentylphenyl)-N-(pyridin-3-yl)acetamide Drug Info Ki = 7260 nM [529389]
4-butyl-N-(quinolin-3-yl)benzamide Drug Info IC50 = 230 nM [529389]
4-heptyl-N-(pyridin-3-yl)benzamide Drug Info Ki = 1740 nM [529389]
4-(methyl(octyl)amino)-N-(quinolin-3-yl)benzamide Drug Info IC50 = 190 nM [529389]
4-decyl-N-(pyridin-3-yl)benzamide Drug Info Ki = 607 nM [529389]
4-butyl-N-(isoquinolin-5-yl)benzamide Drug Info IC50 = 2400 nM [529389]
4-(cyclohexylamino)-N-(quinolin-3-yl)benzamide Drug Info IC50 = 10000 nM [529389]
4-nonyl-N-(quinolin-3-yl)benzamide Drug Info Ki = 980 nM [529389]
4-butyl-N-phenylbenzamide Drug Info Ki = 6272 nM [529389]
4-(butyl(methyl)amino)-N-(quinolin-3-yl)benzamide Drug Info IC50 = 66 nM [529389]
N-methyl-4-pentyl-N-(pyridin-3-yl)benzamide Drug Info Ki = 15000 nM [529389]
(R)-1-(1H-indazol-4-yl)-3-(1-p-tolylethyl)urea Drug Info IC50 = 73 nM [528843]
4-butyl-N-(7-hydroxynaphthalen-1-yl)benzamide Drug Info IC50 = 42 nM [529389]
4-heptyl-N-(quinolin-3-yl)benzamide Drug Info Ki = 3520 nM [529389]
4-octyl-N-(quinolin-3-yl)benzamide Drug Info Ki = 2080 nM [529389]
4-tert-butyl-N-(quinolin-3-yl)benzamide Drug Info IC50 = 41 nM [529389]
4-hexyl-N-(quinolin-3-yl)benzamide Drug Info IC50 = 150 nM [529389]
Action against Disease Model SB-705498 Using a Ca(2+)-based fluorometric imaging plate reader (FLIPR) assay, SB-705498 was shown to be a potent competitive antagonist of the capsaicin-mediated activation of the h uMan TRPV1 receptor (pK(i) = 7.6) with activity at rat (pK(i) = 7.5) and guinea pig (pK(i) = 7.3) orthologs. Whole-cell patch-clamp electrophysiology was used to confirm and extend these findings, demonstrating that SB-705498 can potently inhibit the multiple modes of receptor activation that may be relevant to the pathophysiological role of TRPV1 in vivo: SB-705498 caused rapid and reversible inhibition of the capsaicin (IC(50) = 3 nM)-, acid (pH 5.3)-, or heat (50 degrees C; IC(50) = 6 nM)-mediated activation of h uMan TRPV1 (at -70 mV). [552689] Drug Info
The Effect of Target Knockout, Knockdown or Genetic Variations Bleomycin treatment induced marked cutaneous thickening and fibrosis compared with that observed in control mice treated with PBS. The composite sclerosis score was 18% higher, dermal thickness was 19% higher, the n uMber of alpha-SMA-positive cells was 47% higher, and the amount of hydroxyproline was 57% higher in TRPV1(-/-) mice than in their WT counterparts. Similarly, the composite sclerosis score was 47% higher, dermal thickness was 29% higher, the n uMber of alpha-SMA-positive cells was 76% higher, and the amount of hydroxyproline was 30% higher in CGRP(-/-) mice than in the respective WT groups.These results suggest that activation of the TRPV1 receptor by mediators of inflammation induces sensory neuropeptide release, which might exert protective action against fibrosis [552879]
References
Ref 552879Recent progress in the development of selective TRPV1 antagonists for pain. Curr Top Med Chem. 2008;8(16):1431-41.
Ref 529209J Med Chem. 2008 Jan 10;51(1):57-67. Epub 2007 Dec 12.Stereospecific high-affinity TRPV1 antagonists: chiral N-(2-benzyl-3-pivaloyloxypropyl) 2-[4-(methylsulfonylamino)phenyl]propionamide analogues.
Ref 527363J Med Chem. 2005 Jan 13;48(1):71-90.Discovery of potent, orally available vanilloid receptor-1 antagonists. Structure-activity relationship of N-aryl cinnamides.
Ref 527001Bioorg Med Chem Lett. 2004 Apr 5;14(7):1693-6.N-4-methansulfonamidobenzyl-N'-2-substituted-4-tert-butyl-benzyl thioureas as potent vanilloid receptor antagonistic ligands.
Ref 528843Bioorg Med Chem Lett. 2007 Jul 15;17(14):3894-9. Epub 2007 May 3.Alpha-methylation at benzylic fragment of N-aryl-N'-benzyl ureas provides TRPV1 antagonists with better pharmacokinetic properties and higher efficacy in inflammatory pain model.
Ref 529389Bioorg Med Chem Lett. 2008 Apr 15;18(8):2730-4. Epub 2008 Mar 5.N-pyridin-3-yl- and N-quinolin-3-yl-benzamides: modulators of human vanilloid receptor 1 (TRPV1).
Ref 529389Bioorg Med Chem Lett. 2008 Apr 15;18(8):2730-4. Epub 2008 Mar 5.N-pyridin-3-yl- and N-quinolin-3-yl-benzamides: modulators of human vanilloid receptor 1 (TRPV1).
Ref 530533Bioorg Med Chem. 2010 Jan 1;18(1):111-6. Epub 2009 Nov 10.Silicon switch approach in TRPV1 antagonist MK-056 and its analogues.
Ref 529389Bioorg Med Chem Lett. 2008 Apr 15;18(8):2730-4. Epub 2008 Mar 5.N-pyridin-3-yl- and N-quinolin-3-yl-benzamides: modulators of human vanilloid receptor 1 (TRPV1).
Ref 552879Recent progress in the development of selective TRPV1 antagonists for pain. Curr Top Med Chem. 2008;8(16):1431-41.
Ref 528915J Med Chem. 2007 Jul 26;50(15):3528-39. Epub 2007 Jun 22.Novel vanilloid receptor-1 antagonists: 3. The identification of a second-generation clinical candidate with improved physicochemical and pharmacokinetic properties.
Ref 527423J Med Chem. 2005 Feb 10;48(3):744-52.Novel transient receptor potential vanilloid 1 receptor antagonists for the treatment of pain: structure-activity relationships for ureas with quinoline, isoquinoline, quinazoline, phthalazine, quinoxaline, and cinnoline moieties.
Ref 527623J Med Chem. 2005 Jul 14;48(14):4663-9.The taming of capsaicin. Reversal of the vanilloid activity of N-acylvanillamines by aromatic iodination.
Ref 528909J Med Chem. 2007 Jul 26;50(15):3651-60. Epub 2007 Jun 21.In vitro structure-activity relationship and in vivo characterization of 1-(aryl)-3-(4-(amino)benzyl)urea transient receptor potential vanilloid 1 antagonists.
Ref 528334Bioorg Med Chem Lett. 2006 Oct 1;16(19):5217-21. Epub 2006 Jul 25.From arylureas to biarylamides to aminoquinazolines: discovery of a novel, potent TRPV1 antagonist.
Ref 552689Characterization of SB-705498, a potent and selective vanilloid receptor-1 (VR1/TRPV1) antagonist that inhibits the capsaicin-, acid-, and heat-mediated activation of the receptor. J Pharmacol Exp Ther. 2007 Jun;321(3):1183-92. Epub 2007 Mar 28.
Ref 527623J Med Chem. 2005 Jul 14;48(14):4663-9.The taming of capsaicin. Reversal of the vanilloid activity of N-acylvanillamines by aromatic iodination.
Ref 530533Bioorg Med Chem. 2010 Jan 1;18(1):111-6. Epub 2009 Nov 10.Silicon switch approach in TRPV1 antagonist MK-056 and its analogues.
Ref 530533Bioorg Med Chem. 2010 Jan 1;18(1):111-6. Epub 2009 Nov 10.Silicon switch approach in TRPV1 antagonist MK-056 and its analogues.
Ref 528825J Med Chem. 2007 May 31;50(11):2589-96. Epub 2007 May 10.The potential of transient receptor potential vanilloid type 1 channel modulators for the treatment of pain.
Ref 527001Bioorg Med Chem Lett. 2004 Apr 5;14(7):1693-6.N-4-methansulfonamidobenzyl-N'-2-substituted-4-tert-butyl-benzyl thioureas as potent vanilloid receptor antagonistic ligands.
Ref 531210Bioorg Med Chem. 2010 Nov 15;18(22):8092-105. Epub 2010 Sep 18.Halogenation of 4-hydroxy/amino-3-methoxyphenyl acetamide TRPV1 agonists showed enhanced antagonism to capsaicin.
Ref 528334Bioorg Med Chem Lett. 2006 Oct 1;16(19):5217-21. Epub 2006 Jul 25.From arylureas to biarylamides to aminoquinazolines: discovery of a novel, potent TRPV1 antagonist.
Ref 529279Eur J Med Chem. 2009 Jan;44(1):432-6. Epub 2007 Dec 28.Rare dipeptide and urea derivatives from roots of Moringa oleifera as potential anti-inflammatory and antinociceptive agents.
Ref 528843Bioorg Med Chem Lett. 2007 Jul 15;17(14):3894-9. Epub 2007 May 3.Alpha-methylation at benzylic fragment of N-aryl-N'-benzyl ureas provides TRPV1 antagonists with better pharmacokinetic properties and higher efficacy in inflammatory pain model.
Ref 528843Bioorg Med Chem Lett. 2007 Jul 15;17(14):3894-9. Epub 2007 May 3.Alpha-methylation at benzylic fragment of N-aryl-N'-benzyl ureas provides TRPV1 antagonists with better pharmacokinetic properties and higher efficacy in inflammatory pain model.
Ref 552879Recent progress in the development of selective TRPV1 antagonists for pain. Curr Top Med Chem. 2008;8(16):1431-41.
Ref 552895Clinical development of TRPV1 antagonists: targeting a pivotal point in the pain pathway. Drug Discov Today. 2009 Jan;14(1-2):56-67. doi: 10.1016/j.drudis.2008.11.005. Epub 2008 Dec 26.
Ref 529162J Med Chem. 2007 Dec 27;50(26):6554-69. Epub 2007 Nov 21.New N-arachidonoylserotonin analogues with potential "dual" mechanism of action against pain.
Ref 529162J Med Chem. 2007 Dec 27;50(26):6554-69. Epub 2007 Nov 21.New N-arachidonoylserotonin analogues with potential "dual" mechanism of action against pain.
Ref 529162J Med Chem. 2007 Dec 27;50(26):6554-69. Epub 2007 Nov 21.New N-arachidonoylserotonin analogues with potential "dual" mechanism of action against pain.
Ref 529652Bioorg Med Chem. 2008 Sep 15;16(18):8516-25. Epub 2008 Aug 7.Tetrahydropyridine-4-carboxamides as novel, potent transient receptor potential vanilloid 1 (TRPV1) antagonists.
Ref 528825J Med Chem. 2007 May 31;50(11):2589-96. Epub 2007 May 10.The potential of transient receptor potential vanilloid type 1 channel modulators for the treatment of pain.
Ref 529233Bioorg Med Chem Lett. 2008 Feb 1;18(3):1072-8. Epub 2007 Dec 10.Synthesis of benzamide derivatives as TRPV1 antagonists.
Ref 529233Bioorg Med Chem Lett. 2008 Feb 1;18(3):1072-8. Epub 2007 Dec 10.Synthesis of benzamide derivatives as TRPV1 antagonists.
Ref 529389Bioorg Med Chem Lett. 2008 Apr 15;18(8):2730-4. Epub 2008 Mar 5.N-pyridin-3-yl- and N-quinolin-3-yl-benzamides: modulators of human vanilloid receptor 1 (TRPV1).
Ref 529389Bioorg Med Chem Lett. 2008 Apr 15;18(8):2730-4. Epub 2008 Mar 5.N-pyridin-3-yl- and N-quinolin-3-yl-benzamides: modulators of human vanilloid receptor 1 (TRPV1).
Ref 529389Bioorg Med Chem Lett. 2008 Apr 15;18(8):2730-4. Epub 2008 Mar 5.N-pyridin-3-yl- and N-quinolin-3-yl-benzamides: modulators of human vanilloid receptor 1 (TRPV1).
Ref 529389Bioorg Med Chem Lett. 2008 Apr 15;18(8):2730-4. Epub 2008 Mar 5.N-pyridin-3-yl- and N-quinolin-3-yl-benzamides: modulators of human vanilloid receptor 1 (TRPV1).
Ref 529389Bioorg Med Chem Lett. 2008 Apr 15;18(8):2730-4. Epub 2008 Mar 5.N-pyridin-3-yl- and N-quinolin-3-yl-benzamides: modulators of human vanilloid receptor 1 (TRPV1).
Ref 529389Bioorg Med Chem Lett. 2008 Apr 15;18(8):2730-4. Epub 2008 Mar 5.N-pyridin-3-yl- and N-quinolin-3-yl-benzamides: modulators of human vanilloid receptor 1 (TRPV1).
Ref 529389Bioorg Med Chem Lett. 2008 Apr 15;18(8):2730-4. Epub 2008 Mar 5.N-pyridin-3-yl- and N-quinolin-3-yl-benzamides: modulators of human vanilloid receptor 1 (TRPV1).
Ref 529389Bioorg Med Chem Lett. 2008 Apr 15;18(8):2730-4. Epub 2008 Mar 5.N-pyridin-3-yl- and N-quinolin-3-yl-benzamides: modulators of human vanilloid receptor 1 (TRPV1).
Ref 529389Bioorg Med Chem Lett. 2008 Apr 15;18(8):2730-4. Epub 2008 Mar 5.N-pyridin-3-yl- and N-quinolin-3-yl-benzamides: modulators of human vanilloid receptor 1 (TRPV1).
Ref 529389Bioorg Med Chem Lett. 2008 Apr 15;18(8):2730-4. Epub 2008 Mar 5.N-pyridin-3-yl- and N-quinolin-3-yl-benzamides: modulators of human vanilloid receptor 1 (TRPV1).
Ref 529389Bioorg Med Chem Lett. 2008 Apr 15;18(8):2730-4. Epub 2008 Mar 5.N-pyridin-3-yl- and N-quinolin-3-yl-benzamides: modulators of human vanilloid receptor 1 (TRPV1).
Ref 529389Bioorg Med Chem Lett. 2008 Apr 15;18(8):2730-4. Epub 2008 Mar 5.N-pyridin-3-yl- and N-quinolin-3-yl-benzamides: modulators of human vanilloid receptor 1 (TRPV1).
Ref 529389Bioorg Med Chem Lett. 2008 Apr 15;18(8):2730-4. Epub 2008 Mar 5.N-pyridin-3-yl- and N-quinolin-3-yl-benzamides: modulators of human vanilloid receptor 1 (TRPV1).
Ref 529389Bioorg Med Chem Lett. 2008 Apr 15;18(8):2730-4. Epub 2008 Mar 5.N-pyridin-3-yl- and N-quinolin-3-yl-benzamides: modulators of human vanilloid receptor 1 (TRPV1).
Ref 528843Bioorg Med Chem Lett. 2007 Jul 15;17(14):3894-9. Epub 2007 May 3.Alpha-methylation at benzylic fragment of N-aryl-N'-benzyl ureas provides TRPV1 antagonists with better pharmacokinetic properties and higher efficacy in inflammatory pain model.
Ref 529389Bioorg Med Chem Lett. 2008 Apr 15;18(8):2730-4. Epub 2008 Mar 5.N-pyridin-3-yl- and N-quinolin-3-yl-benzamides: modulators of human vanilloid receptor 1 (TRPV1).
Ref 529389Bioorg Med Chem Lett. 2008 Apr 15;18(8):2730-4. Epub 2008 Mar 5.N-pyridin-3-yl- and N-quinolin-3-yl-benzamides: modulators of human vanilloid receptor 1 (TRPV1).
Ref 529389Bioorg Med Chem Lett. 2008 Apr 15;18(8):2730-4. Epub 2008 Mar 5.N-pyridin-3-yl- and N-quinolin-3-yl-benzamides: modulators of human vanilloid receptor 1 (TRPV1).
Ref 529389Bioorg Med Chem Lett. 2008 Apr 15;18(8):2730-4. Epub 2008 Mar 5.N-pyridin-3-yl- and N-quinolin-3-yl-benzamides: modulators of human vanilloid receptor 1 (TRPV1).
Ref 529389Bioorg Med Chem Lett. 2008 Apr 15;18(8):2730-4. Epub 2008 Mar 5.N-pyridin-3-yl- and N-quinolin-3-yl-benzamides: modulators of human vanilloid receptor 1 (TRPV1).

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