- P-ISSN 2233-4203
- E-ISSN 2093-8950
- 권한신청
- P-ISSN2233-4203
- E-ISSN2093-8950
논문 상세
Home > 논문 상세
DC23, a Triazolothione Resorcinol Analogue, Is Extensively Metabolized to Glucuronide Conjugates in Human Liver Microsomes
DC23, a Triazolothione Resorcinol Analogue, Is Extensively Metabolized to Glucuronide Conjugates in Human Liver Microsomes
Mass Spectrometry Letters / Mass Spectrometry Letters, (P)2233-4203; (E)2093-8950
2018, v.9 no.1, pp.24-29
https://doi.org/10.5478/MSL.2017.9.1.24
(Kyungpook National University)
(Daegu-Gyeongbuk Medical Innovation Foundation)
(Kyungpook National University)
(Daegu-Gyeongbuk Medical Innovation Foundation)
(Kyungpook National University)
(Daegu-Gyeongbuk Medical Innovation Foundation)
(Kyungpook National University)
(Daegu-Gyeongbuk Medical Innovation Foundation)
(Kyungpook National University)
Shon,
J. C.,
Joo,
J.,
Lee,
T.,
Kim,
N. D.,
&
Liu,
K.
(2018). DC23, a Triazolothione Resorcinol Analogue, Is Extensively Metabolized to Glucuronide Conjugates in Human Liver Microsomes. Mass Spectrometry Letters, 9(1), 24-29, https://doi.org/10.5478/MSL.2017.9.1.24
- 다운로드 수
- 조회수
Abstract
DC23, a triazolothione resorcinol analogue, is known to inhibit heat shock protein 90 and pyruvate dehydrogenase kinase which are up-regulated in cancer and diabetes, respectively. This study was performed to elucidate the metabolism of DC23 in human liver microsomes (HLMs). HLMs incubated with DC23 in the presence of uridine 5’-diphosphoglucuronic acid (UDPGA) and/or β-nicotinamide adenine dinucleotide phosphate (NADPH) resulted in the formation of four metabolites, M1- M4. M1 was identified as DC23-N-Oxide, on the basis of LC-MS/MS analysis. DC23 was further metabolized to its glucuronide conjugates (M2, M3, and M4). In vitro metabolic stability studies conducted with DC23 in HLMs revealed significant glucuron- ide conjugation with a t 1/2 value of 1.3 min. The inhibitory potency of DC23 on five human cytochrome P450s was also investi- gated in HLMs. In these experiments, DC23 inhibited CYP2C9-mediated tolbutamide hydroxylase activity with an IC 50 value of 8.7 µM, which could have implications for drug interactions.
- keywords
- DC23, microsomes, oxidation, glucuronidation, drug interaction
참고문헌
1
Sidera, K.. (2014). . Recent Pat Anticancer Drug Discov, 9, 1-.
2
3
4
5
6
Jeong, J. H.. (2016). . Eur. J. Med. Chem., 124, 1069-. http://dx.doi.org/10.1016/j.ejmech.2016.10.038.
7
Fuhrmann-Stroissnigg, H.. (2017). . Nat. Commun., 8, 422-. http://dx.doi.org/10.1038/s41467-017-00314-z.
8
정주희. (2017). Chalcone-templated Hsp90 inhibitors and their effects on gefitinib resistance in non-small cell lung cancer (NSCLC). Archives of Pharmacal Research, 40(1), 96-105.
9
10
11
12
Sharp, S. Y.. (2007). . Mol. Cancer Ther., 6, 1198-. http://dx.doi.org/10.1158/1535-7163.MCT-07-0149.
13
Feldman, R. I.. (2009). . Chem. Biol. Drug Des., 74, 43-. http://dx.doi.org/10.1111/j.1747-0285.2009.00833.x.
14
15
16
17
18
- 투고일Submission Date
- 2018-02-08
- 수정일Revised Date
- 2018-02-21
- 게재확정일Accepted Date
- 2018-02-21
권호 내 다른 논문
- Recent Progress on Microfluidic Electrophoresis Device Application in Mass Spectrometry
- Structural Analysis of [Cu(II)-amyloidogenic peptide] Complexes
- DC23, a Triazolothione Resorcinol Analogue, Is Extensively Metabolized to Glucuronide Conjugates in Human Liver Microsomes
- Direct Quantitation of Amino Acids in Human Serum Using a Stepwise- Dilution Strategy and a Mixed-Mode Liquid Chromatography-Tandem Mass Spectrometry Method
- Observations on Fragmentation Pathway of Farinomalein and its Isomers by Structural Investigation Using LC-MS/MS
- more
추천 논문
학술지 홈페이지 이용 환경은 크롬 브라우저 사용을 권장합니다.