盐酸表柔比星glucuronidation是由人类UDP-glucuronosyltransferase催化2 b7。

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Innocenti F,艾耶L,拉米雷斯J,绿色医学博士Ratain乔丹

盐酸表柔比星glucuronidation是由人类UDP-glucuronosyltransferase催化2 b7。

药物金属底座Dispos。2001; 29 (5): 686 - 92。

PubMed ID

11302935 (在PubMed

]

文摘

盐酸表柔比星是乳腺癌最活跃的代理。盐酸表柔比星的形成由肝脏UDP-glucuronosyltransferase葡糖苷酸(UGT)是其主要的灭活途径。本研究旨在探讨盐酸表柔比星glucuronidation在人类肝微粒体,确定具体UGT同种型,这个反应,并关联表柔比星glucuronidation与其他UGT基质。从人类肝脏微粒体。ugt具体表现在蜂窝系统,以及两个UGT2B7变体,是筛查表柔比星glucuronidation。盐酸表柔比星、吗啡和SN-38葡糖苷酸被高压液相色谱法测量。美国南达科他州的意思是+ / -形成的表柔比星葡糖苷酸在人类肝微粒体(n = 47) 138 + / - 37 pmol /分钟/毫克(变异系数,24%)。这种表型是正态分布。我们筛选商用UGT1A1 UGT1A3 UGT1A4, UGT1A6, UGT1A9, UGT2B7, UGT2B15盐酸表柔比星glucuronidation。只有UGT2B7转换表柔比星葡糖苷酸。 No differences in epirubicin glucuronidation were found in HK293 cells expressing the two UGT2B7 variants at position 268. Catalytic efficiency (V(max)/K(m)) of epirubicin glucuronidation was 1.4 microl/min/mg, a value higher than that observed for morphine, a substrate of UGT2B7. Formation of epirubicin glucuronide was significantly related to that of morphine-3-glucuronide (r = 0.76, p < 0.001) and morphine-6-glucuronide (r = 0.73, p < 0.001). No correlation was found with SN-38, a substrate of UGT1A1 (r = 0.04). UGT2B7 is the major human UGT catalyzing epirubicin glucuronidation, and UGT2B7 is the candidate gene for this phenotype. The reported tyrosine to histidine polymorphism in UGT2B7 does not alter the formation rate of epirubicin glucuronide, and undiscovered genetic polymorphisms in UGT2B7 might change the metabolic fate of this important anticancer agent.

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药物酶

药物	酶	类	生物	药理作用	行动
盐酸表柔比星	UDP-glucuronosyltransferase 2 b7	蛋白质	人类	未知的	底物	细节