Tazofelone
(Synonyms: LY 213829) 目录号 : GC64025
Tazofelone (LY 213829) 是一种环氧合酶-II (COX-II) 抑制剂。Tazofelone 转化为亚砜和喹啉代谢物主要由 CYP3A 介导。Tazofelone 可用于炎症性肠病的研究。
Cas No.:107902-67-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Tazofelone (LY 213829) is a cyclooxygenase-II (COX-II) inhibitor. Tazofelone transform into sulfoxide and quinol metabolites is primarily mediated by CYP3A. Tazofelone can be used for the research of inflammatory bowel disease[1][2].
[1]. Leopold Franz Goetze,et al. Cox- ii inhibitors for improving reproductive success in a female animal. Patent: WO2007129169 A2.
[2]. Surapaneni SS, et al. In vitro biotransformation and identification of human cytochrome P450 isozyme-dependent metabolism of tazofelone. Drug Metab Dispos. 1997 Dec;25(12):1383-8.
| Cas No. | 107902-67-0 | SDF | Download SDF |
| 别名 | LY 213829 | ||
| 分子式 | C18H27NO2S | 分子量 | 321.48 |
| 溶解度 | DMSO : 100 mg/mL (311.06 mM; Need ultrasonic) | 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 | 3.1106 mL | 15.5531 mL | 31.1061 mL |
| 5 mM | 0.6221 mL | 3.1106 mL | 6.2212 mL |
| 10 mM | 0.3111 mL | 1.5553 mL | 3.1106 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。
In vitro biotransformation and identification of human cytochrome P450 isozyme-dependent metabolism of Tazofelone
Drug Metab Dispos 1997 Dec;25(12):1383-8.PMID:9394028doi
Tazofelone is a new inflammatory bowel disease agent. The biotransformation of Tazofelone in human livers and the cytochrome P450 responsible for the biotransformation has been studied. Two metabolites of Tazofelone were formed in vitro. A sulfoxide metabolite was identified by cochromatography with authentic standards, and a quinol metabolite of Tazofelone was identified by mass spectrometry and proton NMR. Sulfoxidation was catalyzed by a single enzyme system while formation of the quinol metabolite was catalyzed by a two enzyme system. The Km and Vmax values for sulfoxidation were 12.4 microM and 0.27 nmol/min/mg protein, respectively. The high affinity Km and Vmax values for the formation of the quinol metabolite were 7.5 microM and 0.17 nmol/min/mg protein, respectively. Tazofelone was incubated at 20 microM concentration with human microsomes to determine which of the cytochrome P450 isozyme(s) is involved in the oxidation of Tazofelone. A strong correlation was found between the immunoquantified concentrations of CYP3A and the rates of formation of the sulfoxide and quinol metabolites of Tazofelone. Similarly, significant correlations were observed between the formation of midazolam 1'-hydroxylation and the rates of formation of both metabolites of Tazofelone. Inhibition studies have indicated that triacetyloleandomycin, a CYP3A specific inhibitor, almost completely inhibited the formation of both of these Tazofelone metabolites. Incubations with specific cDNA expressed microsomes indicated that the formation of both the sulfoxide and quinol metabolites was highest with CYP3A4 containing microsomes. The correlation data was confirmed by inhibition studies and cDNA expressed cytochrome P450 systems demonstrating that the biotransformation of Tazofelone to its metabolites is primarily mediated by CYP3A.
Stereoselective metabolism of Tazofelone, an anti-inflammatory bowel disease agent, in rats and dogs and in human liver microsomes
Chirality 1999;11(3):233-40.PMID:10079502DOI:10.1002/(SICI)1520-636X(1999)11:3<233::AID-CHIR10>3.0.CO;2-J.
Incubation of (R)-tazofelone and (S)-tazofelone in rat, dog, and human liver microsomes demonstrated that the (R)-tazofelone enantiomer was more rapidly metabolized, with two diastereomeric sulfoxides as the major metabolites formed in all three species. The two diasteresomers epimerized at physiological pH, therefore total sulfoxide formation rates were measured. The formation of the total sulfoxide metabolites followed Michaelis-Menten kinetics. The K(m), Vmax, and intrinsic formation clearance (Vmax/K(m)) values were determined in rat, dog, and human liver microsomes. The intrinsic formation clearance of sulfoxide from (R)-tazofelone exceeded that of (S)-tazofelone in all three species. In vivo studies in rats and dogs dosed orally and intravenously confirmed the stereoselective metabolism of Tazofelone observed in vitro. Plasma concentrations of (S)-tazofelone exceeded (R)-tazofelone in rats and dogs by a factor of 3 to 4. In rat portal plasma, both enantiomers were of approximately equal concentration after oral dosing, indicating similar absorption. The half-lives of Tazofelone and total sulfoxides in rats were 3.5 and 2.8 h, respectively. In dogs, the half-lives of Tazofelone and total sulfoxides were 2.2 and 5.5 h, respectively. Plasma clearance was 2.3 l/h in rats and 1.4 l/h in dogs, and the volumes of distribution were 12 and 4.5 l, respectively, in rats and dogs. Both enantiomers were highly bound to plasma proteins to a similar extent in both species.
Discovery of a solid solution of enantiomers in a racemate-forming system by seeding
J Am Chem Soc 2006 Sep 13;128(36):11985-92.PMID:16953640DOI:10.1021/ja063450l.
A racemic liquid of opposite enantiomers usually crystallizes as a racemic compound (racemate), rarely as a conglomerate, and even more rarely as a solid solution. We discovered a Type II solid solution (mixed crystal) of the enantiomers of the chiral drug Tazofelone (TZF) by seeding its racemic liquid with enantiomerically pure crystals (enantiomorphs). Without seeding, the racemic liquid crystallized as a racemic compound. The crystal structure of this solid solution resembles that of the enantiomorph but has static disorder arising from the random substitution of enantiomers. This solid solution is a kinetic product of crystallization made possible by its faster growth rate compared to that of the competing racemate (by 4- to 40-fold between 80 and 146 degrees C). The free energy of the solid solution continuously varies with the enantiomeric composition between those of the conglomerate and the racemates. The existence of the TZF solid solution explains the absence of eutectic melting between crystals of different enantiomeric compositions. The ability of TZF to simultaneously form racemate and solid solution originates from its conformational flexibility. Similar solid solutions of enantiomers may exist in other systems and may be discovered in similar ways. The study demonstrates the use of cross-nucleation for discovering and engineering crystalline materials to optimize physical properties.
Measuring free-energy difference between crystal polymorphs through eutectic melting
J Phys Chem B 2005 Oct 27;109(42):19915-22.PMID:16853575DOI:10.1021/jp053653g.
We describe a method to measure the free-energy difference, DeltaG, between crystal polymorphs from their calorimetric data of eutectic melting with a common additive. The use of different additives yields DeltaG as a function of temperature. The method is suitable for crystals that chemically decompose or physically transform before melting. It applies to not only true polymorphs but also pairs of racemate and conglomerate of resolvable enantiomers. We illustrate the method with the polymorphs of glycine, d-mannitol, and Tazofelone and report a new value (123 degrees C) for the enantiotropic transition temperature of alpha and gamma glycine. We show how different additives (including a liquid additive, water) can be used for different compounds. The DeltaG data thus obtained are important for structure-stability studies and controlling crystallization in polymorphic systems.