Trifluoperazine N-Glucuronide
(Synonyms: 三氟拉嗪N-Β-D-葡糖苷酸,UGT1A4) 目录号 : GC49217
A metabolite of trifluoperazine
Cas No.:165602-90-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >70.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Trifluoperazine N-glucuronide is a metabolite of the antipsychotic agent trifluoperazine .1,2 It is formed from trifluoperazine by the UDP-glucuronosyltransferase (UGT) isoform UGT1A4.2
1.Luo, H., Hawes, E.M., McKay, G., et al.N(+)-glucuronidation of aliphatic tertiary amines in human: antidepressant versus antipsychotic drugsXenobiotica25(3)291-301(1995) 2.Fujiwara, R., Nakajima, M., Yamanaka, H., et al.Interactions between human UGT1A1, UGT1A4, and UGT1A6 affect their enzymatic activitiesDrug Metab. Dispos.35(10)1781-1787(2007)
| Cas No. | 165602-90-4 | SDF | |
| 别名 | 三氟拉嗪N-Β-D-葡糖苷酸,UGT1A4 | ||
| Canonical SMILES | C[N+](CC1)([C@H]2[C@H](O)[C@@H](O)[C@@H]([C@@H](C([O-])=O)O2)O)CCN1CCCN3C4=CC(C(F)(F)F)=CC=C4SC5=CC=CC=C53 | ||
| 分子式 | C27H32F3N3O6S | 分子量 | 583.6 |
| 溶解度 | Methanol: soluble,Water: soluble | 储存条件 | -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 | 1.7135 mL | 8.5675 mL | 17.135 mL |
| 5 mM | 0.3427 mL | 1.7135 mL | 3.427 mL |
| 10 mM | 0.1714 mL | 0.8568 mL | 1.7135 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。
Interactions between human UGT1A1, UGT1A4, and UGT1A6 affect their enzymatic activities
Drug Metab Dispos 2007 Oct;35(10):1781-7.PMID:17620344DOI:10.1124/dmd.107.016402.
Protein-protein interactions between human UDP-glucuronosyltransferase (UGT) 1A1, UGT1A4, and UGT1A6 were investigated using double expression systems in HEK293 cells (UGT1A1/UGT1A4, UGT1A1/UGT1A6, and UGT1A4/UGT1A6). The substrates specific for UGT1A1 (estradiol and bilirubin), UGT1A4 (imipramine and trifluoperazine), and UGT1A6 (serotonin and diclofenac) were used to determine the effects of the coexpression of the other UGT1A isoforms on the enzymatic activity. The coexpression of UGT1A4 and UGT1A6 decreased the S(50) and V(max) values of UGT1A1-catalyzed estradiol 3-O-glucuronide formation and increased the V(max) value of UGT1A1-catalyzed bilirubin O-glucuronide formation. The coexpression of UGT1A1 decreased the V(max) value of UGT1A4-catalyzed imipramine N-glucuronide formation but had no effect on UGT1A4-catalyzed Trifluoperazine N-Glucuronide formation. The coexpression of UGT1A6 had no effect on UGT1A4-catalyzed imipramine N-glucuronide formation but increased the K(m) and V(max) of UGT1A4-catalyzed Trifluoperazine N-Glucuronide formation. The coexpression of both UGT1A1 and UGT1A4 increased the V(max) values of UGT1A6-catalyzed serotonin and diclofenac O-glucuronide formation. Thus, the effects of the coexpression of other UGT1A isoforms on the kinetics of specific activities were different depending on the UGT1A isoforms and substrates. Native polyacrylamide gel electrophoresis analysis of the double expression systems showed multiple bands at approximately 110 kDa, indicating the existence of heterodimers as well as homodimers of UGTs. In conclusion, we found that human UGT1A1, UGT1A4, and UGT1A6 interact with each other, possibly by heterodimerization, and that their effects on the enzymatic activities are complex depending on the isoforms and substrates.
Cabozantinib Carries the Risk of Drug-Drug Interactions via Inhibition of UDPglucuronosyltransferase (UGT) 1A9
Curr Drug Metab 2022;23(11):912-919.PMID:36306450DOI:10.2174/1389200224666221028140652.
Background: Cabozantinib is a multiple receptor tyrosine kinases inhibitor (TKI) approved to treat progressive, metastatic medullary thyroid cancer, advanced renal cell carcinoma, and hepatocellular carcinoma. Drugdrug interactions (DDIs) for cabozantinib have been identified involving the role of cytochromes P450. Although the previous study reported that cabozantinib showed a slight inhibition of UDP-glucuronosyltransferase (UGT) 1A1 at the highest concentration tested, there are no reports on the potential for UGTs-mediated-DDIs. Hence, the current study aims to address this knowledge gap. Objective: This study aimed to investigate the inhibitory effect of cabozantinib on human UGTs and to quantitatively evaluate the DDI potential via UGT inhibition. Methods: The inhibitory effects of cabozantinib on UGTs were determined by measuring the formation rates for 4- methylumbelliferone (4-MU) glucuronide and Trifluoperazine N-Glucuronide using recombinant human UGT isoforms in the absence or presence of cabozantinib. Inhibition kinetic studies were conducted to determine the type of inhibition of cabozantinib on UGTs and the corresponding inhibition constant (Ki) value. In vitro-in vivo extrapolation (IVIVE) was further employed to predict the potential risk of DDI in vivo. Results: Cabozantinib displayed potent inhibition of UGT1A1, 1A3, 1A4, 1A6, 1A7, 1A8, 1A9, 1A10, 2B7, and 2B15. Cabozantinib exhibited noncompetitive inhibition towards UGT1A1 and 1A3 and inhibition towards UGT1A7 and 1A9. The Ki,u values (mean ± standard deviation) were calculated to be 2.15±0.11 μM, 0.83±0.05 μM, 0.75±0.04 μM and 0.18 ± 0.10 μM for UGT1A1, 1A3, 1A7 and 1A9, respectively. Co-administration of cabozantinib at the clinically approved dose of 60 mg/day or 140 mg/day may result in approximately a 26% to 60% increase in the systemic exposure of drugs predominantly cleared by UGT1A9, implying a high risk of DDIs. Conclusion: Cabozantinib has the potential to cause DDIs via the inhibition of UGT1A9; therefore, additional attention should be paid to the safety of the combined use of cabozantinib and drugs metabolized by UGT1A9.