http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
( Jung Yoon Yune ),( Hyeon Liu Kwang ) 한국응용생명화학회 2011 Applied Biological Chemistry (Appl Biol Chem) Vol.54 No.5
Although selective inhibitors of cytochrome P450 enzymes can be used to determine relative contributions of the enzymes to xenobiotic metabolism, characterization of CYP2J2 in drug metabolism is more challenging due to lack of selective, well-characterized inhibitors. Thus, selectivity of hydroxyebastine, which has high affinity for recombinant CYP2J2, was studied. The IC50 value of hydroxyebastine in CYP2J2-mediated astemizole O-demethylation activity was lower than that of its structural analog, terfenadine alcohol. Terfenadine alcohol inhibited several other P450 activities, such as CYP2D6, more potently than CYP2J2, and is thus not suitable as a CYP2J2-selective inhibitor. Inhibitory potential values of hydroxyebastine in CYP2J2-catalyzed astemizole O-demethylation, tolbutamide hydroxylation (CYP2C9), S-mephenytoin hydroxylation (CYP2C19), and dextromethorphan O-demethylation (CYP2D6) were 0.45, 2.74, 10.22, and 3.83 μM, respectively. The inhibitory potential of other P450 enzymes, such as CYP1A2, CYP2B6, CYP2E1, and CYP3A, was negligible. Although hydroxyebastine was a relatively potent inhibitor of CYP2J2, it provided a selectivity of only > 6-fold (CYP2J2 vs. other P450s). However,hydroxyebastine can serve as a relatively selective inhibitor of CYP2J2 and can be used to characterize the contribution of CYP2J2 to xenobiotic metabolism due to the lack of a more specific inhibitor.
Yune-Jung Yoon,Kwang-Hyeon Liu 한국응용생명화학회 2011 Applied Biological Chemistry (Appl Biol Chem) Vol.54 No.5
Although selective inhibitors of cytochrome P450 enzymes can be used to determine relative contributions of the enzymes to xenobiotic metabolism, characterization of CYP2J2 in drug metabolism is more challenging due to lack of selective, well-characterized inhibitors. Thus, selectivity of hydroxyebastine, which has high affinity for recombinant CYP2J2, was studied. The IC50 value of hydroxyebastine in CYP2J2-mediated astemizole O-demethylation activity was lower than that of its structural analog, terfenadine alcohol. Terfenadine alcohol inhibited several other P450 activities, such as CYP2D6, more potently than CYP2J2, and is thus not suitable as a CYP2J2-selective inhibitor. Inhibitory potential values of hydroxyebastine in CYP2J2-catalyzed astemizole O-demethylation, tolbutamide hydroxylation (CYP2C9), S-mephenytoin hydroxylation (CYP2C19), and dextromethorphan O-demethylation (CYP2D6) were 0.45, 2.74, 10.22, and 3.83 μM, respectively. The inhibitory potential of other P450 enzymes, such as CYP1A2, CYP2B6,CYP2E1, and CYP3A, was negligible. Although hydroxyebastine was a relatively potent inhibitor of CYP2J2, it provided a selectivity of only > 6-fold (CYP2J2 vs. other P450s). However,hydroxyebastine can serve as a relatively selective inhibitor of CYP2J2 and can be used to characterize the contribution of CYP2J2 to xenobiotic metabolism due to the lack of a more specific inhibitor.
Yoon, Yune-Jung,Liu, Kwang-Hyeon The Korean Society for Applied Biological Chemistr 2011 Applied Biological Chemistry (Appl Biol Chem) Vol.54 No.5
Although selective inhibitors of cytochrome P450 enzymes can be used to determine relative contributions of the enzymes to xenobiotic metabolism, characterization of CYP2J2 in drug metabolism is more challenging due to lack of selective, well-characterized inhibitors. Thus, selectivity of hydroxyebastine, which has high affinity for recombinant CYP2J2, was studied. The $IC_{50}$ value of hydroxyebastine in CYP2J2-mediated astemizole O-demethylation activity was lower than that of its structural analog, terfenadine alcohol. Terfenadine alcohol inhibited several other P450 activities, such as CYP2D6, more potently than CYP2J2, and is thus not suitable as a CYP2J2-selective inhibitor. Inhibitory potential values of hydroxyebastine in CYP2J2-catalyzed astemizole O-demethylation, tolbutamide hydroxylation (CYP2C9), S-mephenytoin hydroxylation (CYP2C19), and dextromethorphan O-demethylation (CYP2D6) were 0.45, 2.74, 10.22, and 3.83${\mu}M$, respectively. The inhibitory potential of other P450 enzymes, such as CYP1A2, CYP2B6, CYP2E1, and CYP3A, was negligible. Although hydroxyebastine was a relatively potent inhibitor of CYP2J2, it provided a selectivity of only > 6-fold (CYP2J2 vs. other P450s). However, hydroxyebastine can serve as a relatively selective inhibitor of CYP2J2 and can be used to characterize the contribution of CYP2J2 to xenobiotic metabolism due to the lack of a more specific inhibitor.
Yoon, Yune-Jung,Kim, Kwon-Bok,Kim, Hyunmi,Seo, Kyung-Ah,Kim, Ho-Sook,Cha, In-June,Kim, Eun-Young,Liu, Kwang-Hyeon,Shin, Jae-Gook American Society for Pharmacology and Experimental 2007 Drug metabolism and disposition: the biological fa Vol.35 No.9
<P>Benidipine is a dihydropyridine calcium antagonist that has been used clinically as an antihypertensive and antianginal agent. It is used clinically as a racemate, containing the (-)-alpha and (+)-alpha isomers of benidipine. This study was performed to elucidate the metabolism of benidipine and its enantiomers in human liver microsomes (HLMs) and to characterize the cytochrome P450 (P450) enzymes that are involved in the metabolism of benidipine. Human liver microsomal incubation of benidipine in the presence of NADPH resulted in the formation of two metabolites, N-desbenzylbenidipine and dehydrobenidipine. The intrinsic clearance (CL(int)) of the formation of N-desbenzylbenidipine and dehydrobenidipine metabolites from (-)-alpha isomer was similar to those from the (+)-alpha isomer (1.9 +/- 0.1 versus 2.3 +/- 2.3 microl/min/pmol P450 and 0.5 +/- 0.2 versus 0.6 +/- 0.6 microl/min/pmol P450, respectively). Correlation analysis between the known P450 enzyme activities and the rate of the formation of benidipine metabolites in the 15 HLMs showed that benidipine metabolism is correlated with CYP3A activity. The P450 isoform-selective inhibition study in liver microsomes and the incubation study of cDNA-expressed enzymes also showed that theN-debenzylation and dehydrogenation of benidipine are mainly mediated by CYP3A4 and CYP3A5. The total CL(int) values of CYP3A4-mediated metabolite formation from (-)-alpha isomer were similar to those from (+)-alpha isomer (17.7 versus 14.4 microl/min/pmol P450, respectively). The total CL(int) values of CYP3A5-mediated metabolite formation from (-)-alpha isomer were also similar to those from (+)-alpha isomer (8.3 versus 11.0 microl/min/pmol P450, respectively). These findings suggest that CYP3A4 and CYP3A5 isoforms are major enzymes contributing to the disposition of benidipine, but stereoselective disposition of benidipine in vivo may be influenced not by stereoselective metabolism but by other factors.</P>
Park, Yune-Jung,Yoo, Seung-Ah,Choi, Susanna,Yoo, Hee-Soo,Yoon, Ho-Sung,Cho, Chul-Soo,Yoo, Ki-Dong,Kim, Wan-Uk Journal of Rheumatology 2013 The Journal of rheumatology Vol.40 No.6
<P><B>Objective.</B></P><P>Dyslipidemia, a risk factor for cardiovascular diseases, is more prevalent in patients with rheumatoid arthritis (RA) than in the general population. We investigated whether single-nucleotide polymorphisms (SNP) modulating low-density lipoprotein (LDL) cholesterol affect susceptibility, severity, and progression of RA.</P><P><B>Methods.</B></P><P>We enrolled 302 patients with RA and 1636 healthy controls, and investigated the SNP modulating LDL cholesterol. Clinical characteristics of RA, serum adipocytokine concentrations, and radiographic severity were analyzed according to genotype score based on the number of unfavorable alleles. The influence of genotype score on radiographic progression was also investigated using multivariable logistic models.</P><P><B>Results.</B></P><P>We identified 3 SNP (rs688, rs693, and rs4420638) modulating LDL cholesterol in Koreans, which correlated well with LDL cholesterol levels in both patients with RA and controls. Among them, 2 SNP, rs688 and rs4420638, were more prevalent in patients with RA than in controls. In patients with RA carrying more unfavorable alleles (genotype score ≥ 3), disease activity measures, serum adipocytokine levels, and radiographic severity were all increased. The genotype score was an independent risk factor for radiographic progression of RA over 2 years, and its effect was greater than the influence of conventional risk factors.</P><P><B>Conclusion.</B></P><P>SNP modulating LDL cholesterol influence the risk, activity, and severity of RA. These results provide the first evidence that genetic mechanisms linked to dyslipidemia may directly contribute to the susceptibility and prognosis of RA, a representative of chronic inflammatory diseases, explaining the high incidence of dyslipidemia in RA.</P>
Kim Hyojin,Yoon Yune-Jung,Kim Hyunmi,Cha Eun-Young,Lee Hye Suk,Kim Jeong-Han,Yi Kyu Yang,Lee Sunkyung,Cheon Hyae Gyeong,Yoo Sung-Eun,Lee Sang-Seop,Shin Jae-Gook,Liu Kwang-Hyeon The Pharmaceutical Society of Korea 2005 Archives of Pharmacal Research Vol.28 No.11
KR-33028 (N-[4-cyano-benzo[b]thiophene-2-carbonyl]guanidine) is a new cardioprotective agent for preventing ischemia-reperfusion injury. This study was performed to identify the metabolic pathway of KR-33028 in human liver microsomes and to compare its metabolism with that of cryopreserved human hepatocytes. Human liver microsomal incubation of KR-33028 in the presence of NADPH and UDPGA resulted in the formation of four metabolites, M1, M2, M3, and M4. M1 and M2 were identified as 5-hydroxy-KR-33028 and 7-hydroxy-KR-33028, respectively, on the basis of LC/MS/MS analysis with the synthesized authentic standard. M3 and M4 were suggested to be dihydroxy-KR-33028 and hydroxy-KR-33028-glucuronide, respectively. Metabolism of KR-33028 in cryopreserved human hepatocytes resulted in the formation of M1, M2, and M4. These data show a good correlation between major metabolites formed in human liver microsomes and cryopreserved human hepatocytes. In addition, KR33028 was found to inhibit moderately the metabolism of CYP1A2 substrates. Based on the results obtained metabolic pathway of KR-33028 is proposed.