| SB705498TRPV1 antagonist,potent and selective |
Sample solution is provided at 25 µL, 10mM.
Nature.2017 Jan 19;541(7637):417-420.
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- Purity = 98.00%
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- MSDS (Material Safety Data Sheet)
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Chemical structure
| Description | SB705498 is an antagonist of TRPV1 with IC50 values of 3 nM, 0.1 nM and 6 nM for hTRPV1, antagonizes capsaicin, acid and heat activation of TRPV1,respectively. | |||||
| Targets | hTRPV1 | |||||
| IC50 | 3 nM | |||||
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| Cas No. | 501951-42-4 | SDF | Download SDF |
| Chemical Name | 1-(2-bromophenyl)-3-[(3R)-1-[5-(trifluoromethyl)pyridin-2-yl]pyrrolidin-3-yl]urea | ||
| Canonical SMILES | C1CN(CC1NC(=O)NC2=CC=CC=C2Br)C3=NC=C(C=C3)C(F)(F)F | ||
| Formula | C17H16BrF3N4O | M.Wt | 429.23 |
| Solubility | ≥14.5mg/mL in DMSO | Storage | Store at -20°C |
| Physical Appearance | A solid | Shipping Condition | Evaluation sample solution : ship with blue ice.All other available size:ship with RT , or blue ice upon request |
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. | ||
PKi: 7.6 for human TRPV1 receptor
Vanilloid receptor-1 (TRPV1) is a nonselective cation channel, predominantly expressed by sensory neurons, playing a key role in the detection of noxious painful stimuli such as capsaicin, heat, and acid. TRPV1 antagonists may represent novel therapeutic agents for the treatment of a range of conditions including chronic pain, gastrointestinal disorders, and migraine. SB-705498 is a potent, selective and orally bioavailable TRPV1 antagonist.
In vitro: Using a Ca2+-based fluorometric imaging plate reader (FLIPR) assay, SB-705498 was shown to be a potent competitive antagonist of the capsaicin-mediated activation of the human TRPV1 receptor (pKi = 7.6) with activity at rat (pKi = 7.5) and guinea pig (pKi = 7.3) orthologs. SB-705498 caused rapid and reversible inhibition of the capsaicin (IC50 = 3 nM)-, acid (pH 5.3)-, or heat (50°C; IC50 = 6 nM)-mediated activation of human TRPV1 (at =70 mV) [1].
In vivo: Having initially demonstrated that SB-705498 showed good overall in vitro efficacy and oral bioavailability in rat, the in vivo activity of SB-705498 was investigated in the capsaicin-induced secondary hyperalgesia model9 in the rat. This model demonstrates the compound’s antagonist activity in vivo against the specific TRPV1 agonist capsaicin. As an early indicator of potential pharmacodynamic activity, SB-705498 showed excellent activity at 10 and 30 mg/kg po with good reversal of allodynia. Furthermore, SB-705498 was also shown to give 80% reversal of allodynia in the guinea pig FCA model at 10 mg/kg po [2].
Clinical trial: A randomised challenge trial showed that the 3% topical SB705498 cream was clinically well tolerated and had target specific pharmacodynamic activity. However there were no clinically significant differences on pruritus induced by either challenge agent in comparison to placebo. Thus, SB705498 is unlikely to be of symptomatic benefit for histaminergic or non-histaminergic induced itch [3].
Reference:[1] Gunthorpe MJ, Hannan SL, Smart D, Jerman JC, Arpino S, Smith GD, Brough S, Wright J, Egerton J, Lappin SC, Holland VA, Winborn K, Thompson M, Rami HK, Randall A, Davis JB. 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. [2] Rami HK, Thompson M, Stemp G, Fell S, Jerman JC, Stevens AJ, Smart D, Sargent B, Sanderson D, Randall AD, Gunthorpe MJ, Davis JB. Discovery of SB-705498: a potent, selective and orally bioavailable TRPV1 antagonist suitable for clinical development. Bioorg Med Chem Lett. 2006 Jun 15;16(12):3287-91. [3] Gibson RA, Robertson J, Mistry H, McCallum S, Fernando D, Wyres M, Yosipovitch G. A randomised trial evaluating the effects of the TRPV1 antagonist SB705498 on pruritus induced by histamine, and cowhage challenge in healthy volunteers. PLoS One. 2014 Jul 21;9(7):e100610.
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大多数药物在体内都是和特异性受体相互作用，改变细胞的生理生化功能而产生效应。目前已经确定的受体有30多种，根据受体存在的标准，受体可大致分为三类：
1．细胞膜受体：位于靶细胞膜上，如胆碱受体、肾上腺素受体、多巴胺受体、阿片受体等。
2．胞浆受体：位于靶细胞的胞浆内，如肾上腺皮质激素受体、性激素受体。
3．胞核受体：位于靶细胞的细胞核内，如甲状腺素受体。
另外也可根据受体的蛋白结构、信息转导过程、效应性质、受体位置等特点将受体分为四类：
1．含离子通道的受体（离子带受体）：如N-型乙酰胆碱受体含钠离子通道。
2．G蛋白偶联受体：M-乙酰胆碱受体、肾上腺素受体等。
3．具有酪氨酸激酶活性的受体：如胰岛素受体。
4．调节基因表达的受体（核受体）：如甾体激素受体、甲状腺激素受体等。
有些受体具有亚型，各种受体都有特定的分布部位核特定的功能，有些细胞也有多种受体。
请教各位大神，我最近在做WB，565KD的蛋白，动物组织的样品，听说样品制备需要蔗糖裂解液，请问这个是必须的嘛？用一般蛋白提取方法制备可以吗？还有电泳和转膜条件能否分享一下。不胜感激
