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 552879 | Recent progress in the development of selective TRPV1 antagonists for pain. Curr Top Med Chem. 2008;8(16):1431-41. | ||||
Ref 529209 | J 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 527363 | J 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 527001 | Bioorg 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 528843 | Bioorg 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 529389 | Bioorg 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 529389 | Bioorg 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 530533 | Bioorg 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 529389 | Bioorg 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 552879 | Recent progress in the development of selective TRPV1 antagonists for pain. Curr Top Med Chem. 2008;8(16):1431-41. | ||||
Ref 528915 | J 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 527423 | J 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 527623 | J 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 528909 | J 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 528334 | Bioorg 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 552689 | Characterization 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 527623 | J 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 530533 | Bioorg 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 530533 | Bioorg 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 528825 | J 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 527001 | Bioorg 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 531210 | Bioorg 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 528334 | Bioorg 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 529279 | Eur 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 528843 | Bioorg 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 528843 | Bioorg 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 552879 | Recent progress in the development of selective TRPV1 antagonists for pain. Curr Top Med Chem. 2008;8(16):1431-41. | ||||
Ref 552895 | Clinical 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 529162 | J 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 529162 | J 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 529162 | J 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 529652 | Bioorg 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 528825 | J 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 529233 | Bioorg Med Chem Lett. 2008 Feb 1;18(3):1072-8. Epub 2007 Dec 10.Synthesis of benzamide derivatives as TRPV1 antagonists. | ||||
Ref 529233 | Bioorg Med Chem Lett. 2008 Feb 1;18(3):1072-8. Epub 2007 Dec 10.Synthesis of benzamide derivatives as TRPV1 antagonists. | ||||
Ref 529389 | Bioorg 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 529389 | Bioorg 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 529389 | Bioorg 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 529389 | Bioorg 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 529389 | Bioorg 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 529389 | Bioorg 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 529389 | Bioorg 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 529389 | Bioorg 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 529389 | Bioorg 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 529389 | Bioorg 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 529389 | Bioorg 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 529389 | Bioorg 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 529389 | Bioorg 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 529389 | Bioorg 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 528843 | Bioorg 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 529389 | Bioorg 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 529389 | Bioorg 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 529389 | Bioorg 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 529389 | Bioorg 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 529389 | Bioorg 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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