Selective inhibitory effects of HYIpro‐3‐1 on CYP1A2 in human liver microsomes
| العنوان: | Selective inhibitory effects of HYIpro‐3‐1 on CYP1A2 in human liver microsomes |
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| المؤلفون: | Eung-Seok Lee, Tae Cheon Jeong, Ju-Hyun Kim, Tae-Ho Lee, Sangkyu Lee, Younah Kim, Jong-Sup Bae |
| المصدر: | Biopharmaceutics & Drug Disposition. 42:35-41 |
| بيانات النشر: | Wiley, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Cytochrome P-450 CYP1A2 Inhibitors, Pharmaceutical Science, 030226 pharmacology & pharmacy, 03 medical and health sciences, 0302 clinical medicine, Non-competitive inhibition, Cytochrome P-450 CYP1A1, medicine, Humans, Pharmacology (medical), Pharmacology, chemistry.chemical_classification, biology, Secondary plot, CYP1A2, Cytochrome P450, General Medicine, Metabolism, Enzyme, Biochemistry, chemistry, Phenacetin, 030220 oncology & carcinogenesis, Microsomes, Liver, biology.protein, Microsome, medicine.drug |
| الوصف: | CYP1A2 is one of the main Cytochrome P450 enzymes in the human liver associated with the metabolism of several xenobiotics. CYP1A2 is especially involved in the metabolic activation of different procarcinogens. Therefore, the development of cancer may be inhibited by inhibiting CYP1A2 activity. Here, the inhibitory effect of HYIpro-3-1 and its derivatives on CYP1A2 activity in human liver microsomes (HLM) was studied through LC-MS/MS using a cocktail assay. Among the four compounds, HYIpro-3-1 showed the most selective and strongest inhibitory effect on CYP1A2 at IC50 values of 0.1 µM in HLMs and inhibition was confirmed using purified human CYP1A2. It was determined that inhibition is reversible because the inhibitory effect of HYIpro-3-1 is not dependent on preincubation time. HYIpro-3-1 showed a typical pattern of competitive inhibition for CYP1A2-catalyzed phenacetin O-deethylation, based on the Lineweaver-Burk plot, with a Ki value of 0.05 μM in HLMs; the secondary plot also showed a linear pattern. In our study, HYIpro-3-1 was proposed as a novel inhibitor with the capacity to selectively inhibit CYP1A activity in HLMs. This article is protected by copyright. All rights reserved. |
| تدمد: | 1099-081X 0142-2782 |
| DOI: | 10.1002/bdd.2259 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4c337a28bc592f550f0e1e2dcb444a06 https://doi.org/10.1002/bdd.2259 |
| Rights: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....4c337a28bc592f550f0e1e2dcb444a06 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1099081X 01422782 |
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| DOI: | 10.1002/bdd.2259 |