Lactisole
(Synonyms: 2-(4-甲氧基苯氧基)丙酸,na-PMP) 目录号 : GC44024
A sweet taste receptor antagonist
Cas No.:150436-68-3
Sample solution is provided at 25 µL, 10mM.
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- Purity: >98.00%
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Lactisole is an antagonist of sweet taste receptors, reducing both sweetness intensity and persistence. [1][2] It blocks the activation of the sweet taste receptor T1R3 by natural and synthetic sweeteners and increases the inhibition of T1R2 by umami compounds. [3][4] Lactisole can be used to explore the roles of these receptors in diverse pathways, including glucose-induced insulin secretion in pancreatic β-cells and the secretion of glucagon-like peptides by enteroendocrine L-cells. [3][5][6]
Reference:
[1]. Johnson, C., Birch, G.G., and MacDougall, D.B. The effect of the sweetness inhibitor 2(-4-methoxyphenoxy)propanoic acid (sodium salt) (Na-PMP) on the taste of bitter-sweet stimuli. Chem.Senses 19(4), 348-358 (1994).
[2]. Schiffman, S.S., Booth, B.J., Sattely-Miller, E.A., et al. Selective inhibition of sweetness by the sodium salt of ±2-(4-methoxyphenoxy)propanoic acid. Chem.Senses 24(4), 439-447 (1999).
[3]. Hamano, K., Nakagawa, Y., Ohtsu, Y., et al. Lactisole inhibits the glucose-sensing receptor T1R3 expressed in mouse pancreatic β-cells. Journal of Endocrinology 226(1), 57-66 (2015).
[4]. Shim, J., Son, H.J., Kim, Y., et al. Modulation of sweet taste by umami compounds via sweet taste receptor subunit hT1R2. PLoS One 10(4), (2015).
[5]. Ohtsu, Y., Nakagawa, Y., Nagasawa, M., et al. Diverse signaling systems activated by the sweet taste receptor in human GLP-1-secreting cells. Molecular and Cellular Endocrinology 394(1-2), 70-79 (2014).
[6]. Sato, S., Hokari, R., Kurihara, C., et al. Dietary lipids and sweeteners regulate glucagon-like peptide-2 secretion. Am. J. Physiol Gastrointest. Liver Physiol. 304(8), 304-308 (2013).
| Cas No. | 150436-68-3 | SDF | |
| 别名 | 2-(4-甲氧基苯氧基)丙酸,na-PMP | ||
| 化学名 | 2-(4-methoxyphenoxy)-propanoic acid, monosodium salt | ||
| Canonical SMILES | COC1=CC=C(OC(C)C([O-])=O)C=C1.[Na+] | ||
| 分子式 | C10H11O4•Na | 分子量 | 218.2 |
| 溶解度 | 10mg/mL in DMSO,20mg/mL in DMF, 1mg/mL in Ethanol | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 4.583 mL | 22.9148 mL | 45.8295 mL |
| 5 mM | 0.9166 mL | 4.583 mL | 9.1659 mL |
| 10 mM | 0.4583 mL | 2.2915 mL | 4.583 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Impact of Lactisole on the time-intensity profile of selected sweeteners in dependence of the binding site
Food Chem X 2022 Sep 16;15:100446.PMID:36211761DOI:10.1016/j.fochx.2022.100446.
Currently, there is limited insight into the influence of the different binding sites of agonists and antagonists of the sweet taste receptor TAS1R2/TAS1R3 on temporal sensory properties of sweet tasting compounds. We investigated whether the binding site and a competitive or allosteric inhibition of TAS1R2/TAS1R3 influence the time-dependent sensory perception and in vitro TAS1R2/TAS1R3-activation profiles. We compared time-intensity ratings of cyclamate, NHDC, acesulfame K, and aspartame with and without Lactisole with the corresponding TAS1R2/TAS1R3-activation in transfected HEK293 cells. In combination with Lactisole, cyclamate and NHDC demonstrated a shift of the dose-response curve corresponding to a competitive inhibition by Lactisole in the sensory and the cell experiments. Allosteric inhibition by Lactisole for aspartame and acesulfame K was seen in the cell experiments, but not the sensory ratings. In conclusion, the data do not support a major impact of the binding site on the time-intensity profile of the tested sweeteners.
Lactisole inhibits the glucose-sensing receptor T1R3 expressed in mouse pancreatic β-cells
J Endocrinol 2015 Jul;226(1):57-66.PMID:25994004DOI:10.1530/JOE-15-0102.
Glucose activates the glucose-sensing receptor T1R3 and facilitates its own metabolism in pancreatic β-cells. An inhibitor of this receptor would be helpful in elucidating the physiological function of the glucose-sensing receptor. The present study was conducted to examine whether or not Lactisole can be used as an inhibitor of the glucose-sensing receptor. In MIN6 cells, in a dose-dependent manner, Lactisole inhibited insulin secretion induced by sweeteners, acesulfame-K, sucralose and glycyrrhizin. The IC50 was ∼4 mmol/l. Lactisole attenuated the elevation of cytoplasmic Ca2+ concentration ([Ca2+]c) evoked by sucralose and acesulfame-K but did not affect the elevation of intracellular cAMP concentration ([cAMP]c) induced by these sweeteners. Lactisole also inhibited the action of glucose in MIN6 cells. Thus, Lactisole significantly reduced elevations of intracellular [NADH] and intracellular [ATP] induced by glucose, and also inhibited glucose-induced insulin secretion. To further examine the effect of Lactisole on T1R3, we prepared HEK293 cells stably expressing mouse T1R3. In these cells, sucralose elevated both [Ca2+]c and [cAMP]c. Lactisole attenuated the sucralose-induced increase in [Ca2+]c but did not affect the elevation of [cAMP]c. Finally, Lactisole inhibited insulin secretion induced by a high concentration of glucose in mouse islets. These results indicate that the mouse glucose-sensing receptor was inhibited by Lactisole. Lactisole may be useful in assessing the role of the glucose-sensing receptor in mouse pancreatic β-cells.
Differential modulation of the Lactisole 'Sweet Water Taste' by sweeteners
PLoS One 2017 Jul 10;12(7):e0180787.PMID:28700634DOI:10.1371/journal.pone.0180787.
Pre-exposure to taste stimuli and certain chemicals can cause water to have a taste. Here we studied further the 'sweet water taste' (SWT) perceived after exposure to the sweet taste inhibitor Lactisole. Experiment 1 investigated an incidental observation that presenting Lactisole in mixture with sucrose reduced the intensity of the SWT. The results confirmed this observation and also showed that rinsing with sucrose after Lactisole could completely eliminate the SWT. The generalizability of these findings was investigated in experiment 2 by presenting 5 additional sweeteners before, during, or after exposure to Lactisole. The results found with sucrose were replicated with fructose and cyclamate, but the 3 other sweeteners were less effective suppressors of the SWT, and the 2 sweeteners having the highest potency initially enhanced it. A third experiment investigated these interactions on the tongue tip and found that the Lactisole SWT was perceived only when water was actively flowed across the tongue. The same experiment yielded evidence against the possibility that suppression of the SWT following exposure to sweeteners is an aftereffect of receptor activation while providing additional support for a role of sweetener potency. Collectively these results provide new evidence that complex inhibitory and excitatory interactions occur between Lactisole and agonists of the sweet taste receptor TAS1R2-TAS1R3. Receptor mechanisms that may be responsible for these interactions are discussed in the context of the current model of the SWT and the possible contribution of allosteric modulation.
Lactisole interacts with the transmembrane domains of human T1R3 to inhibit sweet taste
J Biol Chem 2005 Apr 15;280(15):15238-46.PMID:15668251DOI:10.1074/jbc.M414287200.
The detection of sweet-tasting compounds is mediated in large part by a heterodimeric receptor comprised of T1R2+T1R3. Lactisole, a broad-acting sweet antagonist, suppresses the sweet taste of sugars, protein sweeteners, and artificial sweeteners. Lactisole's inhibitory effect is specific to humans and other primates; Lactisole does not affect responses to sweet compounds in rodents. By heterologously expressing interspecies combinations of T1R2+T1R3, we have determined that the target for Lactisole's action is human T1R3. From studies with mouse/human chimeras of T1R3, we determined that the molecular basis for sensitivity to Lactisole depends on only a few residues within the transmembrane region of human T1R3. Alanine substitution of residues in the transmembrane region of human T1R3 revealed 4 key residues required for sensitivity to Lactisole. In our model of T1R3's seven transmembrane helices, Lactisole is predicted to dock to a binding pocket within the transmembrane region that includes these 4 key residues.
Asymmetric Synthesis of Photophore-Containing Lactisole Derivatives to Elucidate Sweet Taste Receptors
Molecules 2020 Jun 17;25(12):2790.PMID:32560345DOI:10.3390/molecules25122790.
Lactisole, which has a 2-phenoxy propionic acid skeleton, is well-known as an inhibitor of sweet taste receptors. We recently revealed some of the structure-activity relationships of the aromatic ring and chiral center of Lactisole. Photoaffinity labeling is one of the common chemical biology methods to elucidate the interaction between bioactive compounds and biomolecules. In this paper, the novel asymmetric synthesis of Lactisole derivatives with common photophores (benzophenone, azide and trifluoromethyldiazirine) for photoaffinity labeling is described. The synthetic compounds are subjected to cell-based sweet taste receptors, and the substitution with trifluoromethyldiazirinyl photophore shows the highest affinity to the receptor of the synthesized compounds.