SB-366791

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SB-366791

本产品不向个人销售，仅用作科学研究，不用于任何人体实验及非科研性质的动物实验。

CAS NO:	472981-92-3
规格:	≥98%

包装与价格：

包装	价格(元)
5mg	电议
10mg	电议
25mg	电议
50mg	电议
100mg	电议
250mg	电议
500mg	电议
1g	电议

产品介绍

SB-366791 is a competitive and selective cinnamide TRPV1 (Vanilloid receptor 1) antagonist identified via high-throughput screening of a large chemical library. SB-366791 has IC50 of 5.7±1.2 nM. SB-366791 showed a concentration-dependent potentiation of pH 5-induced 45Ca2+uptake in CHO cells expressing rat TRPV1 but not in untransfected cells. In a FLIPR-based Ca(2+)-assay, SB-366791 produced a concentration-dependent inhibition of the response to capsaicin with an apparent pK(b) of 7.74 +/- 0.08. Schild analysis indicated a competitive mechanism of action with a pA2 of 7.71. In electrophysiological experiments, SB-366791 was demonstrated to be an effective antagonist of hTRPV1 when activated by different modalities, such as capsaicin, acid or noxious heat (50 degrees C). Unlike capsazepine, SB-366791 was also an effective antagonist vs. the acid-mediated activation of rTRPV1. In summary, SB-366791 is a new TRPV1 antagonist with high potency and an improved selectivity profile with respect to other commonly used TRPV1 antagonists. SB-366791 may therefore prove to be a useful tool to further study the biology of TRPV1.

理化性质和储存条件

Molecular Weight (MW)	287.74
Formula	C16H14ClNO2
CAS No.	472981-92-3
Storage	-20℃ for 3 years in powder form
Storage	-80℃ for 2 years in solvent
Solubility (In vitro)	DMSO: ≥ 39 mg/mL
	Water: < 1 mg/mL
	Ethanol: < 1 mg/mL
Solubility (In vivo)	O=C(NC1=CC=CC(OC)=C1)/C=C/C2=CC=C(Cl)C=C2
Synonyms	SB-366791; SB 366791; SB366791

实验参考方法

In Vitro	In vitro activity: SB-366791 is a novel, potent, competitive and selective, cinnamide TRPV1 (Vanilloid receptor 1) antagonist isolated via high-throughput screening of a large chemical library. SB-366791 has IC50 of 5.7±1.2 nM. SB-366791 showed a concentration-dependent potentiation of pH 5-induced 45Ca2+uptake in CHO cells expressing rat TRPV1 but not in untransfected cells. In a FLIPR-based Ca(2+)-assay, SB-366791 produced a concentration-dependent inhibition of the response to capsaicin with an apparent pK(b) of 7.74 +/- 0.08. Schild analysis indicated a competitive mechanism of action with a pA2 of 7.71. In electrophysiological experiments, SB-366791 was demonstrated to be an effective antagonist of hTRPV1 when activated by different modalities, such as capsaicin, acid or noxious heat (50 degrees C). Unlike capsazepine, SB-366791 was also an effective antagonist vs. the acid-mediated activation of rTRPV1. In summary, SB-366791 is a new TRPV1 antagonist with high potency and an improved selectivity profile with respect to other commonly used TRPV1 antagonists. SB-366791 may therefore prove to be a useful tool to further study the biology of TRPV1. Kinase Assay: SB-366791 is a novel, potent, competitive and selective, cinnamide TRPV1 (Vanilloid receptor 1) antagonist isolated via high-throughput screening of a large chemical library. SB-366791 has IC50 of 5.7±1.2 nM. Cell Assay: In a FLIPR-based Ca(2+)-assay, SB-366791 produced a concentration-dependent inhibition of the response to capsaicin with an apparent pK(b) of 7.74 +/- 0.08. Schild analysis indicated a competitive mechanism of action with a pA2 of 7.71. In electrophysiological experiments, SB-366791 was demonstrated to be an effective antagonist of hTRPV1 when activated by different modalities, such as capsaicin, acid or noxious heat (50 degrees C). Unlike capsazepine, SB-366791 was also an effective antagonist vs. the acid-mediated activation of rTRPV1. With the aim of defining a useful tool compound, we also profiled SB-366791 in a wide range of selectivity assays. SB-366791 had a good selectivity profile exhibiting little or no effect in a panel of 47 binding assays (containing a wide range of G-protein-coupled receptors and ion channels) and a number of electrophysiological assays including hippocampal synaptic transmission and action potential firing of locus coeruleus or dorsal raphe neurones. Furthermore, unlike capsazepine, SB-366791 had no effect on either the hyperpolarisation-activated current (I(h)) or Voltage-gated Ca(2+)-channels (VGCC) in cultured rodent sensory neurones. In summary, SB-366791 is a new TRPV1 antagonist with high potency and an improved selectivity profile with respect to other commonly used TRPV1 antagonists. SB-366791 may therefore prove to be a useful tool to further study the biology of TRPV1.
In Vivo	Phα1β and SB366791 interact in a synergistic manner to cause antinociception. We found an interaction index (α) of 0.07 for Phα1β and SB366791 when these drugs were injected together intraplantarly, which indicates that in vivo interaction between these drugs is greater than additive interaction. Synergism also occurred when intraplantar SB366791 was administered simultaneously with intrathecal Phα1β (interaction index α=0.06) suggesting a 15 fold rise in potency on the analgesic effect of these drugs when they are added together. It was observed no significant alterations in body temperature of animals treated with this combination regimen. Swiss mice (20–25 g; 5–7 weeks old) were bred in our animal facility and housed at a controlled temperature (22 ± 2 °C) under a 12-h light/dark cycle with standard laboratory chow and tap water available ad libitum. The animals were habituated to the experimental room for at least 2 h prior to experiments. Each animal was used only once. The experiments reported in this study were performed in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals (NIH publications No. 8023, revised 1978) and ethical guidelines for the investigation of experimental pain in conscious animals. The Ethics Committee in experimentation with living animals from the Institute for Education and Research – Hospital Santa Casa, Belo Horizonte authorized all procedures (Protocol 002/2015).
Animal model	Swiss mice (20–25 g; 5–7 weeks old)
Formulation & Dosage	SB-366791 was dissolved in absolute ethanol for stock solutions; Intraplantar (i.p.) injections
References	Neuropharmacology. 2004 Jan;46(1):133-49; Mol Pharmacol. 2005 Dec;68(6):1524-33.