Tazarotenic Acid
(Synonyms: 他扎罗汀酸,AGN 190299) 目录号 : GC45001
An active metabolite of tazarotene
Cas No.:118292-41-4
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
Tazarotenic acid is an active metabolite of tazarotene, an acetylenic retinoid prodrug that induces epidermal hyperplasia with an ED50 value of 100 nM. Tazarotenic acid selectively binds retinoic acid receptors (RAR-β and RAR-γ) in vitro. It has a relatively short elimination half-life of one to two hours and is metabolized by cytochrome P450 (CYP) isoforms CYP2C8, CYP26A1, and CYP26B1.
| Cas No. | 118292-41-4 | SDF | |
| 别名 | 他扎罗汀酸,AGN 190299 | ||
| Canonical SMILES | OC(C1=CC=C(C#CC2=CC(C(C)(C)CCS3)=C3C=C2)N=C1)=O | ||
| 分子式 | C19H17NO2S | 分子量 | 323.4 |
| 溶解度 | DMF: 30 mg/ml,DMSO: 30 mg/ml,DMSO:PBS(pH 7.2) (1:4): 0.2 mg/ml | 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 | 3.0921 mL | 15.4607 mL | 30.9215 mL |
| 5 mM | 0.6184 mL | 3.0921 mL | 6.1843 mL |
| 10 mM | 0.3092 mL | 1.5461 mL | 3.0921 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。
Identification of Tazarotenic Acid as the First Xenobiotic Substrate of Human Retinoic Acid Hydroxylase CYP26A1 and CYP26B1
J Pharmacol Exp Ther 2016 May;357(2):281-92.PMID:26937021DOI:10.1124/jpet.116.232637.
Cytochrome P450 (CYP) 26A1 and 26B1 are heme-containing enzymes responsible for metabolizing all-trans retinoic acid (at-RA). No crystal structures have been solved, and therefore homology models that provide structural information are extremely valuable for the development of inhibitors of cytochrome P450 family 26 (CYP26). The objectives of this study were to use homology models of CYP26A1 and CYP26B1 to characterize substrate binding characteristics, to compare structural aspects of their active sites, and to support the role of CYP26 in the metabolism of xenobiotics. Each model was verified by dockingat-RA in the active site and comparing the results to known metabolic profiles ofat-RA. The models were then used to predict the metabolic sites of Tazarotenic Acid with results verified by in vitro metabolite identification experiments. The CYP26A1 and CYP26B1 homology models predicted that the benzothiopyranyl moiety of Tazarotenic Acid would be oriented toward the heme of each enzyme and suggested that Tazarotenic Acid would be a substrate of CYP26A1 and CYP26B1. Metabolite identification experiments indicated that CYP26A1 and CYP26B1 oxidatively metabolized Tazarotenic Acid on the predicted moiety, with in vitro rates of metabolite formation by CYP26A1 and CYP26B1 being the highest across a panel of enzymes. Molecular analysis of the active sites estimated the active-site volumes of CYP26A1 and CYP26B1 to be 918 Å(3)and 977 Å(3), respectively. Overall, the homology models presented herein describe the enzyme characteristics leading to the metabolism of Tazarotenic Acid by CYP26A1 and CYP26B1 and support a potential role for the CYP26 enzymes in the metabolism of xenobiotics.
Determination of clobetasol propionate, tazarotene and Tazarotenic Acid in Bama mini-pig skin by UPLC-MS/MS: Application to pharmacokinetic and drug-drug interaction studies
J Pharm Biomed Anal 2020 Jul 15;186:113322.PMID:32380355DOI:10.1016/j.jpba.2020.113322.
Tazarotene and clobetasol propionate are efficacious for the treatment of psoriasis. The plasma pharmacokinetic assessments of tazarotene or clobetasol propionate have been reported. However, the pharmacokinetic characteristics of tazarotene and clobetasol propionate in skin when used together have not been studied. In the present study, sensitive and rapid methods were developed for the determination of clobetasol propionate, tazarotene and its active metabolite Tazarotenic Acid in Bama mini-pig skin by UPLC-MS/MS. After homogenization and pretreatment of skin samples, the separation was performed on a WondaSiL C18 column (4.6 × 150 mm, 5 μm) for tazarotene and clobetasol propionate. The separation of Tazarotenic Acid was achieved on a BDS HYPERSIL C18 column (4.6 × 100 mm, 2.4 μm). All the analytes were quantified with positive electrospray ionization and multiple reactions monitoring mode. The assay was validated in the range of 22-1111 ng/g for tazarotene and clobetasol propionate, 2-111 ng/g for Tazarotenic Acid in skin samples. The methods were fully validated to meet the requirements for bioassay in accuracy, precision, recovery, reproducibility, stabilities and matrix effects, and successfully applied to evaluate the novel combination ointment of tazarotene and clobetasol propionate. The obtained intradermal content-time curves characterized the dermal absorption and metabolism features of the combination ointment. It was also found that there was no significant drug-drug interaction trend between tazarotene and clobetasol propionate. The obtained results would be essential for the development and clinical applications of this novel combination ointment.
Cytochrome P450 2C8 and flavin-containing monooxygenases are involved in the metabolism of Tazarotenic Acid in humans
Drug Metab Dispos 2003 Apr;31(4):476-81.PMID:12642475DOI:10.1124/dmd.31.4.476.
Upon oral administration, tazarotene is rapidly converted to Tazarotenic Acid by esterases. The main circulating agent, Tazarotenic Acid is subsequently oxidized to the inactive sulfoxide metabolite. Therefore, alterations in the metabolic clearance of Tazarotenic Acid may have significant effects on its systemic exposure. The objective of this study was to identify the human liver microsomal enzymes responsible for the in vitro metabolism of Tazarotenic Acid. Tazarotenic Acid was incubated with 1 mg/ml pooled human liver microsomes, in 100 mM potassium phosphate buffer (pH 7.4), at 37 degrees C, over a period of 30 min. The microsomal enzymes that may be involved in Tazarotenic Acid metabolism were identified through incubation with microsomes containing cDNA-expressed human microsomal isozymes. Chemical inhibition studies were then conducted to confirm the identity of the enzymes potentially involved in Tazarotenic Acid metabolism. Reversed-phase high performance liquid chromatography was used to quantify the sulfoxide metabolite, the major metabolite of Tazarotenic Acid. Upon incubation of Tazarotenic Acid with microsomes expressing CYP2C8, flavin-containing monooxygenase 1 (FMO1), or FMO3, marked formation of the sulfoxide metabolite was observed. The involvement of these isozymes in Tazarotenic Acid metabolism was further confirmed by inhibition of metabolite formation in pooled human liver microsomes by specific inhibitors of CYP2C8 or FMO. In conclusion, the in vitro metabolism of Tazarotenic Acid to its sulfoxide metabolite in human liver microsomes is mediated by CYP2C8 and FMO.
Simultaneous determination of tazarotene and its active metabolite Tazarotenic Acid in minipig plasma by LC-MS/MS and its application in pharmacokinetic study after topical administration of tazarotene gel
J Chromatogr B Analyt Technol Biomed Life Sci 2015 Jan 26;978-979:173-8.PMID:25550192DOI:10.1016/j.jchromb.2014.11.030.
To study the systemic exposure of tazarotene formulation after topical administration, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of tazarotene and Tazarotenic Acid in minipig plasma. Similar extraction recoveries for both analytes were obtained after the plasma samples were acidified by glacial acetic acid (5%) and extracted by ethyl ether-cyclohexane (4:1, v/v). Separation of the analytes was achieved within a short time by the addition of 0.1% formic acid to the mobile phase. Gradient elution was used to avoid the matrix effect. The method was linear over the concentration range of 10-600 pg/mL for both analytes. The data of intra- and inter-run precision and accuracy were lower than 5.2%, 7.3% and 7.3% for both analytes. The developed method can be applied to investigate the transdermal pharmacokinetics and the systemic exposure of tazarotene formulation after topical administration.
Treatment of warty dyskeratoma with Tazarotenic Acid
J Am Acad Dermatol 2002 Feb;46(2 Suppl Case Reports):S4.PMID:11807455DOI:10.1067/mjd.2002.104963.
A patient with warty dyskeratoma was successfully treated with Tazarotenic Acid gel. We present evidence to support that this did not occur by chance and suggest that Tazarotenic Acid be investigated further for the treatment of similar dyskeratatic disorders.