Clinical Pharmacology in Drug Development
·
2020
·Vol. 10
·期 1
·57-67
·
IF 1.903
Lu-Ning Sun,Guo-Xian Sun,Yu-Qing Yang,Ye Shen,Feng-Ru Huang,Li-Jun Xie,Juan Cheng,Hong-Wen Zhang,Xue-Hui Zhang,Yun Liu,Yong-Qing Wang
Sitafloxacin, a new fluoroquinolone, has strong antibacterial activity. We evaluated the effects of sitafloxacin granules in single-dose and multidose cohorts and the effects of ABCB1, UGT1A1 , and UGT1A9 genetic polymorphisms on the pharmacokinetics (PK) of sitafloxacin in healthy subjects. The single-dose study included 3 fasted cohorts receiving 50, 100, and 200 mg of sitafloxacin granules and 1 cohort receiving 50 mg of sitafloxacin granules with a high-fat meal. The multidose study included 1 cohort receiving 100 mg of sitafloxacin granules once daily for 5 days. PK parameters were calculated using noncompartmental parameters based on concentration-time data. The genotypes for ABCB1 , UGT1A1 , and UGT1A9 single-nucleotide polymorphisms were determined using Sanger sequencing. Subsequently, the association between sitafloxacin PK parameters and target single-nucleotide polymorphisms was analyzed. Sitafloxacin granules were well tolerated up to 200 and 100 mg in the single-dose and multidose studies, respectively. Sitafloxacin AUC and C max increased linearly within the detection range, and a steady state was reached within 3 days after the administration of multiple oral doses. Our findings showed that C max was lower in the ABCB1 (rs1045642) mutation group, whereas t 1/2 was longer in the UGT1A1 (rs2741049) and UGT1A9 (rs3832043) mutation groups. In conclusion, sitafloxacin granules were safe at single doses and multiple doses up to 200 and 100 mg/day, respectively, with a linear plasma PK profile. However, ABCB1 (rs1045642), UGT1A1 (rs2741049), and UGT1A9 (rs3832043) genetic polymorphisms are likely to influence the C max or t 1/2 and thereby merit further clinical evaluation.
研究领域:
药理学
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遗传学
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临床研究
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DOI
PubMed
高影响因子
CURRENT DRUG METABOLISM
·
2022
·Vol. 23
·期 11
·912-919
·
IF 3.408
Wang Zhe,Jiang Lili,Wang Xiaoyu,Yin Hang,Wang Zhen,Lv Xin,Liu Yong
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.
研究领域:
药理学
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临床医学
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生物化学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS
·
2024
·
IF 1.9
Li Wenjing,Xue Yufan,Zhang Feng,Xiao Ling,Huang Zhu,Li Wenjuan,Zhu Liangliang,Ge Guangbo
Background and Objective Ciclopirox is a widely used antifungal drug, redisposition of which has drawn increasing attentions due to multiple promising activities. The drug undergoes extensive glucuronidation, which acts as a major obstacle in the ongoing novel application and still remains poorly understood. The current study aims to phenotype ciclopirox glucuronidation pathway and as well to decipher the related species differences. Methods Ciclopirox glucuronidation was investigated in liver microsomes from humans (HLM) and various experimental animals. Assays with recombinant uridine diphosphate glucuronosyltransferases (UGTs), enzyme kinetic analyses and selective inhibitors were used to determine the role of individual UGTs in ciclopirox glucuronidation. Results HLM is highly active in ciclopirox glucuronidation with Michaelis–Menten constant ( K m ), maximum velocity ( V max ), and intrinsic clearance (CL int ) values of 139 μM, 7.89 nmol/min/mg, and 56 μL/min/mg, respectively. UGT1A9 displays by far the highest activity, whereas several other isoforms (UGT1A6, UGT1A7, and UGT1A8) catalyze formation of traced glucuronides. Further kinetic analysis demonstrates that UGT1A9 has a closed K m value (167 μM) to HLM. UGT1A9 selective inhibitor (magnolol) can potently inhibit ciclopirox glucuronidation in HLM with the IC 50 value of 0.12 μM. The reaction displays remarkable differences across liver microsomes from mice, rats, cynomolgus monkey, minipig, and beagle dog, with the CL int values in the range of 26–369 μL/min/mg. In addition, ciclopirox glucuronidation activities of experimental animals’ liver microsomes were less sensitive to magnolol than that of HLM. Conclusions Ciclopirox glucuronidation displays remarkable species differences with UGT1A9 as a dominant contributor in humans. It is suggested that the pharmacological or toxicological effects of ciclopirox may be UGT1A9 and species dependent.
研究领域:
药理学
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生物化学
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DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL SCIENCES
·
2015
·
IF 2.59
Hua Sun,Zhiguo Ma,Danyi Lu,Baojian Wu
ABSTRACT In th is study, we aimed to determine the glucuronidation potential of psoralidin in humans and to perform validation on use of psoralidin-3- O -glucuronidation as afunctional marker for UGT1A9. Glucuronidation kinetics was determined using human liver microsomes (HLMs), human intestine microsomes (HIM), and expressed UDP-glucuronosyltransferase (UGT) enzymes. The chemical structures of metabolites were determined by liquid chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy analyses. Validation of psoralidin-3- O -glucuronidation as a UGT1A9 marker was performed using combined approaches including reaction phenotyping, chemical inhibition, activity correlation analysis, and determination of relative activity factor (RAF). HLM and UGT1A9 generated two monoglucuronides (9- O -glucuronide and 3- O -glucuronide) from psoralidin, whereas HIM, UGT1A1, UGT1A7, and UGT1A8 generated one only (9- O -glucuronide). Formation of 3- O -glucuronide in HLM was markedly inhibited by the UGT1A9-selective inhibitors magnolol and niflumic acid . Further, psoralidin-3- O -glucuronidation was strongly correlated with propofol-glucuronidation in a group of nine individual HLMs ( r = 0.978, p < 0.001). Strong correlation was also observed between psoralidin-3- O -glucuronidation and the UGT1A9 protein levels measured by Western blotting ( r = 0.944, p < 0.001). Moreover, UGT1A9 was responsible for 99.6% of psoralidin-3- O -glucuronidation in HLM based on the RAF approach. In conclusion, psoralidin was subjected to efficient glucuronidation, generating one or two monoglucuronides depending on UGT isozymes . Also, psoralidin-3- O -glucuronidation was an excellent in vitro marker for UGT1A9.
研究领域:
药理学
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代谢
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酶学
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药物代谢
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DOI
PubMed
高影响因子
PHARMACEUTICAL RESEARCH
·
2013
·Vol. 31
·期 4
·847-860
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IF 4.742
Tang Lan,Li Ye,Chen Wei-Ying,Zeng Shan,Dong Ling-Na,Peng Xiao-Juan,Jiang Wen,Hu Ming,Liu Zhong-Qiu
Purpose UDP-glucuronosyltransferases (UGTs) are responsible for the formation of glucuronides of polyphenolic flavonoids. This study investigated the UGT1A9-mediated glucuronidation of luteolin and the kinetics of luteolin glucuronide efflux. Method HeLa cells overexpressing UGT1A9 (HeLa-UGT1A9) were used to determine the kinetics of breast cancer resistance protein (BCRP)-mediated transport of luteolin glucuronides. Human UGT isoforms were used to determine glucuronidation rates. Results UGT1A9 was found to catalyze the production of four luteolin glucuronides, including three known monoglucuronides and a novel 3′, 4′-diglucuronide. Ko143, a potent specific inhibitor of BCRP, significantly inhibited efflux of luteolin monoglucuronides from HeLa1A9 cells and increased their intracellular levels in a dose-dependent manner. The formation of luteolin diglucuronide was observed when intracellular concentration of total monoglucuronides went above 0.07 nM. Conclusions Intracellular accumulation of diglucuronide was detected at high monoglucuronide concentrations (>0.07 nM). Diglucuronide production is speculated to be a compensatory pathway for luteolin disposition.
研究领域:
药理学
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分子生物学
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DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2011
·Vol. 26
·期 1
·86-90
·
IF 1.878
Rui-Hua Dong,Zhong-Ze Fang,Liang-Liang Zhu,Si-Cheng Liang,Guang-Bo Ge,Ling Yang,Ze-Yuan Liu
UDP-glucuronosyltransferases (UGTs), the most important phase II drug metabolizing enzymes (DMEs), could metabolize many drugs and various endogenous substances including bilirubin, steroid hormones, thyroid hormones, bile acids and fat-soluble vitamins. Evaluation of the inhibitory effects of compounds on UGTs is clinically important because inhibition of UGT isoforms could not only result in serious drug–drug interactions (DDIs), but also induce metabolic disorders of endogenous substances. The aim of the present study was to investigate the inhibitory effects of carvacrol on major UGT isoforms. The results showed that carvacrol could inhibit the activity of UGT1A9 with negligible effects on other UGT isoforms. When 4-methylumbelliferone (4-MU) was used as a nonspecific probe substrate and recombinant UGT enzymes were utilized as an enzyme resource, the inhibition of UGT1A9 was best fit to the competitive type and the inhibition kinetic parameter ( K i ) was calculated to be 5.7 µ m . Furthermore, another specific probe substrate, propofol, was employed to determine the inhibitory kinetics of UGT1A9, and the results demonstrated that the inhibitory type was noncompetitive. The inhibition kinetic parameter ( K i ) was determined to be 25.0 µ m . Because this substrate-dependent inhibition of UGT1A9 might confuse the in vitro–in vivo extrapolation, these in vitro inhibition kinetic parameters should be interpreted with special caution. Copyright © 2011 John Wiley & Sons, Ltd.
研究领域:
药理学
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生物化学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2023
·
IF 7.5
Xueru He,Ying Li,Yajing Li,Caihui Guo,Yuhao Fu,Xuejiao Xun,Zhi Wang,Zhanjun Dong
Donafenib (DONA), a deuterium derivative of sorafenib, is used for advanced hepatocellular carcinoma (HCC). Dapagliflozin (DAPA) and canagliflozin (CANA) are sodium–glucose co-transporter 2 (SGLT2) inhibitors used for T2DM, which is frequently comorbid with HCC. Three drugs are substrates of UGT1A9 isoenzyme. This study aimed to evaluate donafenib–dapagliflozin and donafenib–canagliflozin pharmacokinetic interactions and explore the potential mechanisms. Rats were divided into seven groups (n = 6) that received donafenib (1), dapagliflozin (2), canagliflozin (3), dapagliflozin and donafenib (4), canagliflozin and donafenib (5), donafenib and dapagliflozin (6), donafenib and canagliflozin (7). The concentrations of drugs were determined by an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. The messenger RNA (mRNA) expressions were measured by quantitative RT-PCR. Multiple doses of dapagliflozin caused donafenib maximum plasma concentration (C max ) to increase 37.01%. Canagliflozin increased donafenib C max 1.77-fold and the area under the plasma concentration–time curves (AUC 0−t and AUC inf ) 1.39- and 1.41-fold, respectively, while reducing the apparent clearance (CL z ) 28.38%. Multiple doses of donafenib increased dapagliflozin AUC 0−t 1.61-fold, AUC inf 1.77-fold, whereas its CL z reduced 40.50%. Furthermore, donafenib caused similar changes in canagliflozin pharmacokinetics. The PCR results demonstrated that dapagliflozin inhibited the mRNA expression of Ugt1a7 in liver and donafenib decreased the expression of Ugt1a7 mRNA in liver and intestine. Increased exposure to these drugs may be due to their metabolism inhibition mediated by Ugt1a7. These pharmacokinetic interactions observed in this study may be of clinical significance, which may help adjust dose properly and avoid toxicity effects in patients with HCC and T2DM.
研究领域:
药理学
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肿瘤学
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糖尿病研究
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2022
·
IF 5.112
Le-Yuan Shang,Ming-Hao Zhou,Si-Yuan Cao,Min Zhang,Peng-Jiao Wang,Shuo Zhang,Xiao-Xia Meng,Qi-Mei Yang,Xiu-Li Gao
Baicalin (BG) is a bioactive flavonoid extracted from the dried root of the medicinal plant, Scutellaria radix (SR) (dicotyledonous family, Labiatae), and has several biological activities. Polyethylene glycol 400 (PEG400) has been used as a suitable solvent for several traditional Chinese medicines (TCM) and is often used as an excipient for the compound preparation of SR. However, the drug–excipient interactions between BG and PEG400 are still unknown. Herein, we evaluated the effect of a single intravenous PEG400 administration on the BG levels of rats using pharmacokinetic and tissue distribution studies. A liver microsome and recombinant enzyme incubation system were used to further confirm the interaction mechanism between PEG400 and UDP-glucuronosyltransferases (UGTs) (UGT1A8 and UGT1A9). The pharmacokinetic study demonstrated that following the co-intravenous administration of PEG400 and BG, the total clearance (CL z ) of BG in the rat plasma decreased by 101.60% ( p < 0.05), whereas the area under the plasma concentration-time curve (AUC) 0-t and AUC 0-inf increased by 144.59% ( p < 0.05) and 140.05% ( p < 0.05), respectively. Additionally, the tissue distribution study showed that the concentration of BG and baicalein-6-O-β-D-glucuronide (B6G) in the tissues increased, whereas baicalein (B) in the tissues decreased, and the total amount of BG and its metabolites in tissues altered following the intravenous administration of PEG400. We further found that PEG400 induced the UGT1A8 and UGT1A9 enzyme activities by affecting the maximum enzymatic velocity (V max ) and Michaelis–Menten constant (K m ) values of UGT1A8 and UGT1A9. In conclusion, our results demonstrated that PEG400 interaction with UGTs altered the pharmacokinetic behaviors and tissue distribution characteristics of BG and its metabolites in rats.
研究领域:
药理学
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生物化学
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药物化学
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中药学
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产品关联
DOI
PubMed
高影响因子
Pharmaceuticals
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2021
·Vol. 14
·期 11
·1194
·
IF 5.863
Min Li,Qingfeng He,Li Yao,Xiaofeng Wang,Zhijia Tang,Xiao Zhu,Hai-Shu Lin,Xiaoqiang Xiang
Propylthiouracil (PTU) is commonly prescribed for the management of hyperthyroidism and thyrotoxicosis. Although the exact mechanism of action is not fully understood, PTU is associated with hepatoxicity in pediatric population. Glucuronidation mediated by uridine 5′-diphospho-glucuronosyltransferases (UGTs), which possess age-dependent expression, has been proposed as an important metabolic pathway of PTU. To further examine the metabolism of PTU, a reliable HPLC-MS/MS method for the simultaneous quantification of PTU and its N-β-D glucuronide (PTU-GLU) was developed and validated. The chromatographic separation was achieved on a ZORBAX Extend-C18 column (2.1 × 50 mm, 1.8 μm) through gradient delivery of a mixture of formic acid, methanol and acetonitrile. The electrospray ionization (ESI) was operated in its negative ion mode while PTU and PTU-GLU were detected by multiple reaction monitoring (MRM). This analytical method displayed excellent linearity, sensitivity, accuracy, precision, recovery and stability while its matrix effect and carry-over were insignificant. Subsequently, the in vitro metabolism of PTU was assessed and UGT1A9 was identified as an important UGT isoform responsible for the glucuronidation of PTU. The information obtained from this study will facilitate future mechanistic investigation on the hepatoxicity of PTU and may optimize its clinical application.Keywords:propylthiouracil;propylthiouracil glucuronide;in vitro;human liver microsomes;UGT1A9;HPLC-MS/MS
研究领域:
药理学
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分析化学
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毒理学
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产品关联
DOI
PubMed
高影响因子
PeerJ
·
2020
·
IF 2.379
Xiaoyan Li,Yiyan Lu,Xiaojun Ou,Sijing Zeng,Ying Wang,Xiaoxiao Qi,Lijun Zhu,Zhongqiu Liu
Background This study aimed to systematically profile the alterations and sex- and age-related differences in the drug metabolizing enzymes (DMEs) in a KRAS-mutant mouse model of lung cancer (KRAS mice). Methodology In this study, the LC-MS/MS approach and a probe substrate method were used to detect the alterations in 21 isoforms of DMEs, as well as the enzymatic activities of five isoforms, respectively. Western blotting was applied to study the protein expression of four related receptors. Results The proteins contents of CYP2C29 and CYP3A11, were significantly downregulated in the livers of male KRAS mice at 26 weeks (3.7- and 4.4-fold, respectively, p < 0.05). SULT1A1 and SULT1D1 were upregulated by 1.8- to 7.0- fold at 20 ( p = 0.015 and 0.017, respectively) and 26 weeks ( p = 0.055 and 0.031, respectively). There were positive correlations between protein expression and enzyme activity for CYP2E1, UGT1A9, SULT1A1 and SULT1D1 ( r 2 ≥ 0.5, p < 0.001). Western blotting analysis revealed the downregulation of AHR, FXR and PPARα protein expression in male KRAS mice at 26 weeks. For sex-related differences, CYP2E1 was male-predominant and UGT1A2 was female-predominant in the kidney. UGT1A1 and UGT1A5 expression was female-predominant, whereas UGT2B1 exhibited male-predominant expression in liver tissue. For the tissue distribution of DMEs, 21 subtypes of DMEs were all expressed in liver tissue. In the intestine, the expression levels of CYP2C29, CYP27A1, UGT1A2, 1A5, 1A6a, 1A9, 2B1, 2B5 and 2B36 were under the limitation of quantification. The subtypes of CYP7A1, 1B1, 2E1 and UGT1A1, 2A3, 2B34 were detected in kidney tissue. Conclusions This study, for the first time, unveils the variations and sex- and age-related differences in DMEs in C57 BL/6 (WT) mice and KRAS mice.
研究领域:
药理学
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肿瘤学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
MOLECULES
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2022
·Vol. 27
·期 19
·6190
·
IF 4.927
Xueru He,Ying Li,Yinling Ma,Yuhao Fu,Xuejiao Xun,Yanjun Cui,Zhanjun Dong
Sorafenib (SOR), an inhibitor of multiple kinases, is a classic targeted drug for advanced hepatocellular carcinoma (HCC) which often coexists with type 2 diabetes mellitus (T2DM). Dapagliflozin (DAPA), a sodium–glucose cotransporter-2 inhibitor (SGLT2i), is widely used in patients with T2DM. Notably, co-administration of SOR with DAPA is common in clinical settings. Uridine diphosphate-glucuronosyltransferase family 1 member A9 (UGT1A9) is involved in the metabolism of SOR and dapagliflozin (DAPA), and SOR is the inhibitor of UGT1A1 and UGT1A9 (in vitro). Therefore, changes in UGT1A9 activity caused by SOR may lead to pharmacokinetic interactions between the two drugs. The objective of the current study was to develop an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous determination of SOR and DAPA in plasma and to evaluate the effect of the co-administration of SOR and DAPA on their individual pharmacokinetic properties and the mechanism involved. The rats were divided into four groups: SOR (100 mg/kg) alone and co-administered with DAPA (1 mg/kg) for seven days, and DAPA (1 mg/kg) alone and co-administered with SOR (100 mg/kg) for seven days. Liquid–liquid extraction (LLE) was performed for plasma sample preparation, and the chromatographic separation was conducted on Waters XSelect HSS T3 column with a gradient elution of 0.1% formic acid and 5 mM ammonium acetate (Phase A) and acetonitrile (Phase B). The levels of Ugt1a7 messenger RNA (mRNA) were determined in rat liver and intestine using quantitative real-time polymerase chain reaction (qRT-PCR). The method was successfully applied to the study of pharmacokinetic interactions. DAPA caused a significant decrease in the maximum plasma concentrations (Cmax) and the area under the plasma concentration–time curves (AUC0–t) of SOR by 41.6% and 50.5%, respectively, while the apparent volume of distribution (Vz/F) and apparent clearance (CLz/F) significantly increased 2.85- and 1.98-fold, respectively. When co-administering DAPA with SOR, the AUC0–tand the elimination half-life (t1/2Z) of DAPA significantly increased 1.66- and 1.80-fold, respectively, whereas the CLz/Fsignificantly decreased by 40%. Results from qRT-PCR showed that, compared with control, seven days of SOR pretreatment decreased Ugt1a7 expression in both liver and intestine tissue. In contrast, seven days of DAPA pretreatment decreased Ugt1a7 expression only in liver tissue. Therefore, pharmacokinetic interactions exist between long-term use of SOR with DAPA, and UGT1A9 may be the targets mediating the interaction. Active surveillance for the treatment outcomes and adverse reactions are required.Keywords:UPLC-MS/MS;sorafenib;dapagliflozin;pharmacokinetics;drug–drug interactions
研究领域:
药理学
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临床药学
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分子生物学
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药物代谢
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
·
2022
·
IF 5.011
Liangliang Zhu,Hui Lv,Ling Xiao,Yanyao Hou,Wenjuan Li,Guangbo Ge,Chunzhi Ai
β-estradiol (β-E2) and α-estradiol (α-E2) act as an endo- and an exon-estrogen in humans, respectively. There is a structural variation in C17-OH configuration of the two estrogens. UDP-glucuronosyltransferases (UGT) are responsible for termination of activities of a variety of endogenous hormones, clinical drugs, and environmental toxicants. The current study was conducted to investigate the effects of the two estrogens towards catalytic activities of UGTs. It was found that β-E2 could decrease activities of UGT1A9 , − 2B4 and − 2B7, with K i values of a few micro-molars. β-E2 could additionally accelerate the activity of UGT2B17 via promoting enzyme-substrate binding and increasing the turn over number . Comparatively, α-E2 displayed much stronger inhibitory potentials towards UGT2B7 and − 2B4, but showed little influence to UGT1A9 and − 2B17. The K i values for inhibition of UGT2B7 in glucuronidation of different substrates by α-E2 were in a nanomolar range that is only about 1/100–1/50 of β-E2. UGT2B7 structural model was fatherly constructed to explore the mechanism underlying dramatically different inhibition selectivity of the two estrogens. Compared to β-E2, α-E2 formed more hydrophobic and hydrogen-bonded interactions with the residues in the active pocket. It is concluded that the configuration of E2–17-OH determines the inhibitory potentials towards UGTs. The results are useful in better understanding ligand selectivity of UGTs, as well as in further development of α-E2 in health protection.
研究领域:
药理学
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生物化学
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分子生物学
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内分泌学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）