5'-Iodoresiniferatoxin - CAS 535974-91-5
Category: Inhibitor
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Molecular Formula:
C37H39IO9
Molecular Weight:
754.60
COA:
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Description:
5'-Iodoresiniferatoxin is a very potent and strong competitive antagonist of the transient receptor potential vanilloid 1 (TRPV1) receptor. It is derived from resiniferatoxin (RTX), which is produced by the Moroccan succulent Euphorbia resinifera. It is iodinated at the 5-position and can be prepared from RTX by electrophilic aromatic substitution. It binds to TRPV1 (VR1) receptors expressed in HEK293 cells with Kd value of 4.3 nM and Ki value of 5.8 nM. It binds to the VR1 receptor with high affinity but does not induce RTX- or capsaicin-like effects in Xenopus laevis oocytes expressing VR1. It is 40-fold more potent than capsazepine.
Purity:
≥98% by HPLC
Synonyms:
[(2S,​3aR,​3bS,​6aR,​9aR,​9bR,​10R,​11aR)​-​3a,​3b,​6,​6a,​9a,​10,​11,​11a-​Octahydro-​6a-​hydroxy-​8,​10-​dimethyl-​11a-​(1-​methylethenyl)​-​7-​oxo-​2-​(phenylmethyl)​-​7H-​2,​9b-​epoxyazuleno[5,​4-​e]​-​1,​3-​benzodioxol-​5-​yl]​methyl Ester 4-​Hydroxy-​3-​iodo-​5-​methoxy-benzeneacetic Acid; Iodoresiniferatoxin; 5'-IRTX; 6,7-Deepoxy-6,7-didehydro-5-deoxy-21-dephenyl-21-(phenylmethyl)-daphnetoxin,20-(4-hydroxy-5-iodo-3-methoxybenzeneacetate)
MSDS:
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InChIKey:
TZUJORCXGLGWDV-RYACRXIZSA-N
InChI:
InChI=1S/C37H39IO9/c1-20(2)35-16-22(4)37-26(33(35)45-36(46-35,47-37)18-23-9-7-6-8-10-23)12-25(17-34(42)29(37)11-21(3)32(34)41)19-44-30(39)15-24-13-27(38)31(40)28(14-24)43-5/h6-14,22,26,29,33,40,42H,1,15-19H2,2-5H3/t22-,26+,29-,33-,34-,35-,36?,37-/m1/s1
Canonical SMILES:
CC1CC2(C3C4C1(C5C=C(C(=O)C5(CC(=C4)COC(=O)CC6=CC(=C(C(=C6)I)O)OC)O)C)OC(O3)(O2)CC7=CC=CC=C7)C(=C)C
1.Design of a high-affinity competitive antagonist of the vanilloid receptor selective for the calcium entry-linked receptor population.
Tóth A;Blumberg PM;Chen Z;Kozikowski AP Mol Pharmacol. 2004 Feb;65(2):282-91.
We describe the synthesis and characterization of N-(4-chlorobenzyl) -N'-(4-hydroxy-3-iodo-5-methoxybenzyl)thiourea (IBTU), a novel antagonist of the vanilloid receptor 1 (TRPV1 or VR1). IBTU competitively inhibited 45Ca2+ uptake into CHO cells heterologously expressing rat TRPV1, whether induced by capsaicin or resiniferatoxin (Ki = 99 +/- 23 and 93 +/- 34 nM, respectively). IBTU was thus somewhat more potent (5-fold) than capsazepine. In contrast to its antagonism of vanilloid-induced calcium uptake, IBTU (30 microM) inhibited [3H]resiniferatoxin binding to TRPV1 by less than 10%. We hypothesize that these dramatically distinct potencies reflect different fractions of TRPV1 in this system: namely, a minor plasma membrane fraction controlling 45Ca2+ uptake, and the predominant intracellular fraction that dominates the [3H]resiniferatoxin binding measurements. Intracellular Ca2+ imaging supports this explanation. IBTU antagonized the elevation in intracellular Ca2+ in response to 50 nM capsaicin with an IC50 of 106 +/- 35 nM. Likewise, 600 nM IBTU was able to antagonize the elevation in intracellular Ca2+ in response to 100 pM resiniferatoxin in the presence of normal (1.8 mM) extracellular Ca2+, where the increase in intracellular calcium reflects calcium influx.
2.The carbonate analogues of 5'-halogenated resiniferatoxin as TRPV1 ligands.
Lim KS;Lee H;Kim SE;Ha TH;Ann J;Son K;Choi S;Sun W;Pearce LV;DeAndrea-Lazarus IA;Blumberg PM;Lee J Eur J Med Chem. 2013 Oct;68:233-43. doi: 10.1016/j.ejmech.2013.07.042. Epub 2013 Aug 9.
A series of carbonate analogues of 5'-halogenated RTX have been investigated in order to examine the effect of the carbonate group as a linker and the role of halogens in the reversal of activity from agonism to antagonism for rat and human TRPV1 heterologously expressed in Chinese hamster ovary cells. The carbonate analogues showed similar activities to the corresponding RTX derivatives in rat TRPV1 but lower potency in human TRPV1. 5-Halogenation converted the agonists to partial agonists or full antagonists and the extent of antagonism reflected the order of I>Br>Cl>F, with a somewhat greater extent of antagonism for the derivatives of the 4-amino RTX surrogates compared to the corresponding derivatives of RTX itself. The carbonate analogues of I-RTX (60) and 5-bromo-4-amino-RTX (66) were potent and full antagonists with Ki(ant)=2.23 and 2.46 nM, respectively, for rat TRPV1, which were ca. 5-fold more potent than I-RTX (2) under our conditions. The conformational analysis of the I-RTX-carbonate (60) indicated that its bent conformation was similar to that of I-RTX, consistent with compound 60 and I-RTX showing comparable potent antagonism.
3.Involvement of apoptosis and calcium accumulation through TRPV1 channels in neurobiology of epilepsy.
Nazıroğlu M;Övey İS Neuroscience. 2015 May 7;293:55-66. doi: 10.1016/j.neuroscience.2015.02.041. Epub 2015 Mar 2.
Calcium ion accumulation into the cytosol of the hippocampus and dorsal root ganglion (DRG) are main reasons in etiology of epilepsy. Transient receptor potential vanilloid type 1 (TRPV1) channel is a cation-permeable calcium channel found in the DRG and hippocampus. Although previous studies implicate TRPV1 channels in the generation of epilepsy, suppression of ongoing seizures by TRPV1 antagonists has not yet been investigated. We tested the effects of TRPV1-specific antagonists, capsazepine (CPZ) and 5'-iodoresiniferatoxin (IRTX) on the modulation of calcium accumulation, apoptosis and anticonvulsant properties in the hippocampus and DRG of pentylentetrazol (PTZ) and capsaicin (CAP) administrated rats. Forty rats were divided into five groups as follows; control, PTZ, CAP+PTZ, IRTX, and IRTX+PTZ. Fura-2 and patch-clamp experiments were performed on neurons dissected from treated animals by CAP and CPZ. PTZ and CAP+PTZ administrations increased intracellular free Ca(2+) concentrations, TRPV1 current densities, apoptosis, caspase 3 and 9 values although the values were reduced by IRTX and CPZ treatments. Latency time was extended by application CPZ and IRTX although CAP produced acceleration of epileptic seizures.
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CAS 535974-91-5 5'-Iodoresiniferatoxin

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