Metabolite elucidation of the Hsp90 inhibitor SNX-2112 using ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS)
Metabolite elucidation of the Hsp90 inhibitor SNX-2112 using ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS)
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使用超高效液相色谱/四极杆飞行时间质谱 (UPLC-QTOF/MS) 阐明 Hsp90 抑制剂 SNX-2112 的代谢物
DOI：
10.3109/00498254.2013.853849
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发表时间：
2014-04
期刊：
影响因子：
1.8
通讯作者：
Wu, Baojian
中科院分区：
文献类型：
--
作者：
Dong, Dong;Ma, Zhiguo;Wang, Yifei;Wu, Baojian
1. The novel heat-shock protein 90 inhibitor SNX-2112 is a promising drug candidate for treating various types of cancers. Here we aim to determine the metabolic pathways of SNX-2112 in ratsin vivoand in humansin vitro.2. Metabolite identification was performed using ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) method.In vitrometabolism studies were performed using liver and intestine microsomes, as well as recombinant human cytochrome P450 (CYP) enzymes.3. Analysis of rat plasma, urine, and feces revealed a total of eight metabolites, one reductive metabolite (M1), one structurally unknown metabolite (M2), and six mono-oxidative metabolites (M3-1, M3-2, M3-3, M3-4, M3-5, and M3-6). The reduction, M2, and mono-oxidation pathways were responsible for 0.8 ± 0.3 %, 18.3 ± 9.1 %, and 39.4% ± 6.1 of SNX-2112 clearance from rats, respectively.4. SNX-2112 was subjected to the same types of metabolism in human liver and intestine microsomes. Reaction phenotyping showed that CYP3A4, 3A5, 2D6, and 1A1 were mainly responsible for SNX-2112 metabolism.5. In conclusion, we have elucidated the metabolic pathways of SNX-2112 and highlighted that metabolism was the predominant pathway for its clearance. Better understanding of SNX-2112 metabolism should facilitate the drug development of this promising anti-cancer agent.
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影响因子：
4
作者：
P. Csermely;T. Schnaider;Z. Prohászka;G. Nardai
通讯作者：
P. Csermely;T. Schnaider;Z. Prohászka;G. Nardai
影响因子：
2
作者：
Wrona, M;Mauriala, T;O'Connor, D
通讯作者：
O'Connor, D
影响因子：
4.8
作者：
Walsh, Agnes A.;Szklarz, Grazyna D.;Scott, Emily E.
通讯作者：
Scott, Emily E.
影响因子：
20.3
作者：
Okawa, Yutaka;Hideshima, Teru;Anderson, Kenneth C.
通讯作者：
Anderson, Kenneth C.
影响因子：
2
作者：
Bateman, Kevin P.;Castro-Perez, Jose;Nicoll-Griffith, Deborah A.
通讯作者：
Nicoll-Griffith, Deborah A.