KAT681 (T0681)
(Synonyms: T0681) 目录号 : GC31616
KAT681 (T0681) 是一种肝脏选择性的拟甲状腺素。
Cas No.:373641-87-3
Sample solution is provided at 25 µL, 10mM.
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KAT681 is a liver-selective thyromimetic.
The impact of the liver-selective thyromimetic KAT681 (T-0681) is investigated on lipoprotein metabolism. Prolonged treatment with KAT681 increases the hepatic expression of both low-density lipoprotein (LDL) receptor and scavenger receptor class B, type I without affecting cholesteryl ester transfer protein activity. Western blot showing human SR-BI (CLA-1) expression in normal HepG2 cells and in HepG2 cells loaded with AcLDL and subsequently incubated with vehicle or KAT681. SR-BI protein expression is markedly downregulated by incubation with 50 μg/mL AcLDL. This effect can not be reversed by addition of KAT681[1]
In preliminary dose-titration studies, a marked decrease of plasma cholesterol is observed at 36 nmoles/kg/day KAT681 (T-0681), whereas doses higher than 36 nmoles/kg/day show no further lipid-lowering effect. In the subsequent study, New Zealand White (NZW) rabbits are fed a 0.2% cholesterol diet and dosed with 36 nmoles/kg/day KAT681 or a respective placebo control for 4 weeks. KAT681 treatment results in a 60% decrease of plasma cholesterol and a 70% decrease of plasma triglycerides[1]. In preliminary dose-titration studies in wild-type (WT) mice, a marked increase of hepatic SR-BI expression at 36 nmol/kg/d KAT681 (T-0681), and a concomitant 50% decrease of plasma cholesterol are observed. Higher doses than 36 nmol/kg/d show no further lipid-lowering effect. KAT681 significantly increases hepatic LDLrs in SR-BI KO mice (2-fold of controls, P<0.01), along with a marked decrease in plasma cholesterol[2].
[1]. Tancevski I, et al. The thyromimetic T-0681 protects from atherosclerosis. J Lipid Res. 2009 May;50(5):938-44. [2]. Tancevski I, et al. The liver-selective thyromimetic T-0681 influences reverse cholesterol transport and atherosclerosis development in mice. PLoS One. 2010 Jan 15;5(1):e8722.
Cell experiment: | HepG2 cells are used. At a confluency of 70%, HepG2 cells are incubated with 50 μg/mL of acetylated LDL (AcLDL) for 24 h and subsequently treated with indicated amounts of KAT681 (0.5 μM) in serum-free medium for another 24 h. Cellular protein extraction and Western blot analysis are performed. |
Animal experiment: | Rabbits[1]Male NZW rabbits are subcutaneously implanted with Alzet osmotic pumps carrying KAT681 (36 nmoles/kg/day) in 1% DMSO/PBS or 1% DMSO/PBS alone as control for the entire duration of the studies. Rabbits are fed a 0.2% cholesterol and 3.5% fat diet or a 2% cholesterol and 5% fat diet. Food consumption is restricted to 100 g/day/animal. At the end of the studies, animals are fasted 5 h before the collection of blood samples, killed by a threefold overdose of pentobarbital, and organ biopsies snap-frozen.Mice[2]Male C57/B6 (WT) mice are fed a standard chow diet. After 2 weeks of acclimatization, mice are divided into two groups and subcutaneously implanted with Alzet micro-osmotic pumps carrying KAT681 in PBS (36 nmol/kg/d) or PBS alone as control for 14 days. After 14 days of treatment, animals are fasted for 5 h and anesthetized. Blood samples are taken, mice sacrificed by cervical dislocation, and organ biopsies are snap-frozen. Male SR-BI KO and LDLr KO mice are fed a standard chow diet, and subcutaneously implanted with Alzet micro-osmotic pumps carrying KAT681 in PBS (36 nmol/kg/d) or PBS alone as control. Mice are then fasted for 5 h, blood samples are taken, mice are sacrificed by cervical dislocation, and liver biopsies are snap-frozen. |
References: [1]. Tancevski I, et al. The thyromimetic T-0681 protects from atherosclerosis. J Lipid Res. 2009 May;50(5):938-44. | |
| Cas No. | 373641-87-3 | SDF | |
| 别名 | T0681 | ||
| Canonical SMILES | O=C(O)CC(NC1=CC(C)=C(OC2=CC=C(O)C(C(C3=CC=C(F)C=C3)O)=C2)C(C)=C1)=O.[Na] | ||
| 分子式 | C24H22FNNaO6 | 分子量 | 462.42 |
| 溶解度 | Soluble in DMSO | 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 | 2.1625 mL | 10.8127 mL | 21.6254 mL |
| 5 mM | 0.4325 mL | 2.1625 mL | 4.3251 mL |
| 10 mM | 0.2163 mL | 1.0813 mL | 2.1625 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。
Quality Control & SDS
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- Purity: >98.00%
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