Target Validation Information | |||||
---|---|---|---|---|---|
TTD ID | T83193 | ||||
Target Name | Transient receptor potential cation channel V1 (TRPV1) | ||||
Type of Target |
Successful |
||||
Drug Potency against Target | A-425619 | Drug Info | IC50 = 4 nM | [19] | |
ABT-102 | Drug Info | IC50 = 4 nM | [19] | ||
AMG-517 | Drug Info | IC50 = 0.8 nM | [20] | ||
BCTC | Drug Info | IC50 = 7 nM | [19] | ||
Drug Info | IC50 = 110 nM | [16] | |||
(5E,8E,11E,14E)-Icosa-5,8,11,14-tetraenal | Drug Info | IC50 = 51 nM | [4] | ||
(E)-3-(4-tert-Butyl-phenyl)-N-phenyl-acrylamide | Drug Info | IC50 = 330 nM | [2] | ||
(E)-Octadec-9-enal | Drug Info | IC50 = 35 nM | [4] | ||
(R)-1-(1H-indazol-4-yl)-3-(1-p-tolylethyl)urea | Drug Info | IC50 = 73 nM | [7] | ||
(S)-1-(1H-indazol-4-yl)-3-(1-p-tolylethyl)urea | Drug Info | IC50 = 749 nM | [7] | ||
1,3-dibenzyl urea | Drug Info | IC50 = 10 nM | [13] | ||
1-(4-Bromo-benzyl)-3-quinazolin-8-yl-urea | Drug Info | IC50 = 170 nM | [3] | ||
1-(isoquinolin-5-yl)-3-(1-phenylpropyl)urea | Drug Info | IC50 = 2580 nM | [7] | ||
1-(isoquinolin-5-yl)-3-(4-morpholinobenzyl)urea | Drug Info | IC50 = 91 nM | [8] | ||
1-benzhydryl-3-(isoquinolin-5-yl)urea | Drug Info | IC50 = 600 nM | [7] | ||
2-(4-pentylphenyl)-N-(pyridin-3-yl)acetamide | Drug Info | Ki = 7260 nM | [14] | ||
4-(3-methylpyridin-2-yl)-N-p-tolylbenzamide | Drug Info | IC50 = 2585 nM | [5] | ||
4-(butyl(methyl)amino)-N-(quinolin-3-yl)benzamide | Drug Info | IC50 = 66 nM | [14] | ||
4-(cyclohexylamino)-N-(quinolin-3-yl)benzamide | Drug Info | IC50 = 10000 nM | [14] | ||
4-(hexyl(methyl)amino)-N-(quinolin-3-yl)benzamide | Drug Info | IC50 = 86 nM | [14] | ||
4-(methyl(nonyl)amino)-N-(quinolin-3-yl)benzamide | Drug Info | IC50 = 150 nM | [14] | ||
4-(methyl(octyl)amino)-N-(quinolin-3-yl)benzamide | Drug Info | IC50 = 190 nM | [14] | ||
4-butyl-N-(7-hydroxynaphthalen-1-yl)benzamide | Drug Info | IC50 = 42 nM | [14] | ||
4-butyl-N-(isoquinolin-5-yl)benzamide | Drug Info | IC50 = 2400 nM | [14] | ||
4-butyl-N-(pyridin-3-yl)benzamide | Drug Info | Ki = 626 nM | [14] | ||
4-butyl-N-(quinolin-3-yl)benzamide | Drug Info | IC50 = 230 nM | [14] | ||
4-butyl-N-phenylbenzamide | Drug Info | Ki = 6272 nM | [14] | ||
4-decyl-N-(pyridin-3-yl)benzamide | Drug Info | Ki = 607 nM | [14] | ||
4-heptyl-N-(pyridin-3-yl)benzamide | Drug Info | Ki = 1740 nM | [14] | ||
4-heptyl-N-(quinolin-3-yl)benzamide | Drug Info | Ki = 3520 nM | [14] | ||
4-hexyl-N-(quinolin-3-yl)benzamide | Drug Info | IC50 = 150 nM | [14] | ||
4-nonyl-N-(quinolin-3-yl)benzamide | Drug Info | Ki = 980 nM | [14] | ||
4-octyl-N-(pyridin-3-yl)benzamide | Drug Info | Ki = 546 nM | [14] | ||
4-octyl-N-(quinolin-3-yl)benzamide | Drug Info | Ki = 2080 nM | [14] | ||
4-pentyl-N-pyridin-3-yl benzamide | Drug Info | Ki = 421 nM | [14] | ||
4-propyl-N-(quinolin-3-yl)benzamide | Drug Info | IC50 = 130 nM | [14] | ||
4-Pyridin-2-yl-piperazine-1-carboxylic acid amide | Drug Info | IC50 = 30 nM | [1] | ||
4-tert-butyl-N-(quinolin-3-yl)benzamide | Drug Info | IC50 = 41 nM | [14] | ||
5'-iodoresiniferatoxin | Drug Info | Ki = 12.2 nM | [11] | ||
6'-Iodononivamide | Drug Info | Ki = 127 nM | [17] | ||
A-795614 | Drug Info | IC50 = 30 nM | [15] | ||
AMG-628 | Drug Info | IC50 = 2 nM | [9] | ||
ATC-120 | Drug Info | IC50 = 50 nM | [16] | ||
CAPSAZEPINE | Drug Info | IC50 = 887 nM | [6] | ||
JNJ-17203212 | Drug Info | IC50 = 16 nM | [6] | ||
N-(4-iodophenyl)-4-(trifluoromethoxy)benzamide | Drug Info | IC50 = 280 nM | [12] | ||
N-(4-iodophenyl)-4-(trifluoromethyl)benzamide | Drug Info | IC50 = 330 nM | [12] | ||
N-(4-tert-butylphenyl)-4-(pyridin-2-yl)benzamide | Drug Info | IC50 = 8 nM | [5] | ||
N-methyl-4-pentyl-N-(pyridin-3-yl)benzamide | Drug Info | Ki = 15000 nM | [14] | ||
N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]lauramide | Drug Info | IC50 = 740 nM | [10] | ||
N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]linoleamide | Drug Info | IC50 = 1820 nM | [10] | ||
N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]undecanamide | Drug Info | IC50 = 760 nM | [10] | ||
Pyrrolidin-1-yl-thiourea | Drug Info | IC50 = 3000 nM | [1] | ||
SC-0030 | Drug Info | IC50 = 40 nM | [16] | ||
Action against Disease Model | SB-705498 | Drug Info | 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). | [18] | |
References | |||||
REF 1 | N-4-methansulfonamidobenzyl-N'-2-substituted-4-tert-butyl-benzyl thioureas as potent vanilloid receptor antagonistic ligands. Bioorg Med Chem Lett. 2004 Apr 5;14(7):1693-6. | ||||
REF 2 | Discovery of potent, orally available vanilloid receptor-1 antagonists. Structure-activity relationship of N-aryl cinnamides. J Med Chem. 2005 Jan 13;48(1):71-90. | ||||
REF 3 | Novel transient receptor potential vanilloid 1 receptor antagonists for the treatment of pain: structure-activity relationships for ureas with quin... J Med Chem. 2005 Feb 10;48(3):744-52. | ||||
REF 4 | The taming of capsaicin. Reversal of the vanilloid activity of N-acylvanillamines by aromatic iodination. J Med Chem. 2005 Jul 14;48(14):4663-9. | ||||
REF 5 | From arylureas to biarylamides to aminoquinazolines: discovery of a novel, potent TRPV1 antagonist. Bioorg Med Chem Lett. 2006 Oct 1;16(19):5217-21. | ||||
REF 6 | The potential of transient receptor potential vanilloid type 1 channel modulators for the treatment of pain. J Med Chem. 2007 May 31;50(11):2589-96. | ||||
REF 7 | Alpha-methylation at benzylic fragment of N-aryl-N'-benzyl ureas provides TRPV1 antagonists with better pharmacokinetic properties and higher effic... Bioorg Med Chem Lett. 2007 Jul 15;17(14):3894-9. | ||||
REF 8 | In vitro structure-activity relationship and in vivo characterization of 1-(aryl)-3-(4-(amino)benzyl)urea transient receptor potential vanilloid 1 ... J Med Chem. 2007 Jul 26;50(15):3651-60. | ||||
REF 9 | Novel vanilloid receptor-1 antagonists: 3. The identification of a second-generation clinical candidate with improved physicochemical and pharmacok... J Med Chem. 2007 Jul 26;50(15):3528-39. | ||||
REF 10 | New N-arachidonoylserotonin analogues with potential "dual" mechanism of action against pain. J Med Chem. 2007 Dec 27;50(26):6554-69. | ||||
REF 11 | Stereospecific high-affinity TRPV1 antagonists: chiral N-(2-benzyl-3-pivaloyloxypropyl) 2-[4-(methylsulfonylamino)phenyl]propionamide analogues. J Med Chem. 2008 Jan 10;51(1):57-67. | ||||
REF 12 | Synthesis of benzamide derivatives as TRPV1 antagonists. Bioorg Med Chem Lett. 2008 Feb 1;18(3):1072-8. | ||||
REF 13 | Rare dipeptide and urea derivatives from roots of Moringa oleifera as potential anti-inflammatory and antinociceptive agents. Eur J Med Chem. 2009 Jan;44(1):432-6. | ||||
REF 14 | N-pyridin-3-yl- and N-quinolin-3-yl-benzamides: modulators of human vanilloid receptor 1 (TRPV1). Bioorg Med Chem Lett. 2008 Apr 15;18(8):2730-4. | ||||
REF 15 | Tetrahydropyridine-4-carboxamides as novel, potent transient receptor potential vanilloid 1 (TRPV1) antagonists. Bioorg Med Chem. 2008 Sep 15;16(18):8516-25. | ||||
REF 16 | Silicon switch approach in TRPV1 antagonist MK-056 and its analogues. Bioorg Med Chem. 2010 Jan 1;18(1):111-6. | ||||
REF 17 | Halogenation of 4-hydroxy/amino-3-methoxyphenyl acetamide TRPV1 agonists showed enhanced antagonism to capsaicin. Bioorg Med Chem. 2010 Nov 15;18(22):8092-105. | ||||
REF 18 | Characterization of SB-705498, a potent and selective vanilloid receptor-1 (VR1/TRPV1) antagonist that inhibits the capsaicin-, acid-, and heat-med... J Pharmacol Exp Ther. 2007 Jun;321(3):1183-92. | ||||
REF 19 | Recent progress in the development of selective TRPV1 antagonists for pain. Curr Top Med Chem. 2008;8(16):1431-41. | ||||
REF 20 | Clinical development of TRPV1 antagonists: targeting a pivotal point in the pain pathway. Drug Discov Today. 2009 Jan;14(1-2):56-67. | ||||
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