FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4211132616> ?p ?o ?g. }

• W4211132616 endingPage "289" @default.
• W4211132616 startingPage "261" @default.
• W4211132616 abstract "Ribonucleotide reductase (RR) catalyzes the essential step in the formation of all four deoxynucleotides. Upregulated activity of RR plays an active role in tumor progression. As the regulatory subunit of RR, ribonucleotide reductase subunit M2 (RRM2) is regarded as one of the effective therapeutic targets for DNA replication-dependent diseases, such as cancers. Recent studies have revealed that osalmid significantly inhibits the activity of RRM2, but the metabolic profile of osalmid remains unknown.The aim of this study was to clarify the metabolic profile including metabolites, isoenzymes and metabolic pathways of osalmid. The anti-human hepatocellular carcinoma activity and mechanism of metabolites were further investigated.Ultra high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) was used for identifying metabolites and for characterizing phase I and phase II metabolic pathways with recombinant enzymes or in human liver microsomes of osalmid. The eHiTS docking system was used for potential RRM2 inhibitor screening among metabolites. Cytotoxicity assays were performed for evaluating cell proliferation inhibitory activity of metabolites. Cell cycle assays and cell apoptosis assays were assessed by flow cytometry. Western blotting analysis of RRM2, cyclin D1, p21, p53, phosphorylated p53, Bcl-2 and Bax was performed to explore the anti-hepatocellular carcinoma mechanism of the active metabolites.Ten metabolites of osalmid were identified, and none of them have been reported previously. Hydroxylation, glucuronidation, sulfonation, acetylation and degradation were recognized as the main metabolic processes of osalmid. Isozymes of CYP1A2, CYP2C9, UGT1A1, UGT1A6, UGT1A9, UGT2B7 and UGT2B15 were involved in phase I and phase II metabolism of osalmid. Metabolites M7, M8 and M10 showed higher binding affinities with the RRM2 active site than osalmid. Metabolite M7 exhibited potent inhibitory activity to hepatocellular carcinoma cell lines by both competitive inhibition and down-regulation of RRM2. Moreover, M7 significantly induced cell cycle arrest and apoptosis by activating p53-related pathways.The metabolic profile of osalmid was identified. M7 significantly inhibited human hepatocellular carcinoma progression by inhibiting RRM2 activity. Furthermore, M7 induced cell cycle arrest and apoptosis by activating p53-related signaling pathways." @default.
• W4211132616 created "2022-02-13" @default.
• W4211132616 creator A5028415096 @default.
• W4211132616 creator A5067829318 @default.
• W4211132616 date "1989-01-01" @default.
• W4211132616 modified "2023-10-05" @default.
• W4211132616 title "UDP-glucuronosyltransferases" @default.
• W4211132616 cites W104199933 @default.
• W4211132616 cites W1429527117 @default.
• W4211132616 cites W1483148476 @default.
• W4211132616 cites W1510706283 @default.
• W4211132616 cites W1525939685 @default.
• W4211132616 cites W1527077584 @default.
• W4211132616 cites W1529226096 @default.
• W4211132616 cites W1535379356 @default.
• W4211132616 cites W1537991464 @default.
• W4211132616 cites W1556141382 @default.
• W4211132616 cites W1561943091 @default.
• W4211132616 cites W1566763721 @default.
• W4211132616 cites W1568156879 @default.
• W4211132616 cites W1569367290 @default.
• W4211132616 cites W1577828799 @default.
• W4211132616 cites W162756263 @default.
• W4211132616 cites W1679145101 @default.
• W4211132616 cites W1768362036 @default.
• W4211132616 cites W1822059636 @default.
• W4211132616 cites W1886509899 @default.
• W4211132616 cites W1950804083 @default.
• W4211132616 cites W1962863985 @default.
• W4211132616 cites W1967282710 @default.
• W4211132616 cites W1969276900 @default.
• W4211132616 cites W1971486995 @default.
• W4211132616 cites W1973446780 @default.
• W4211132616 cites W1975974320 @default.
• W4211132616 cites W1980150135 @default.
• W4211132616 cites W1982191241 @default.
• W4211132616 cites W1982558048 @default.
• W4211132616 cites W1983485938 @default.
• W4211132616 cites W1987945988 @default.
• W4211132616 cites W1989278378 @default.
• W4211132616 cites W1990118136 @default.
• W4211132616 cites W1991374252 @default.
• W4211132616 cites W1992450050 @default.
• W4211132616 cites W1993258802 @default.
• W4211132616 cites W1996099484 @default.
• W4211132616 cites W1996249056 @default.
• W4211132616 cites W1997545177 @default.
• W4211132616 cites W1998390265 @default.
• W4211132616 cites W1999940435 @default.
• W4211132616 cites W1999955538 @default.
• W4211132616 cites W2000742403 @default.
• W4211132616 cites W2001441776 @default.
• W4211132616 cites W2001930607 @default.
• W4211132616 cites W2003821417 @default.
• W4211132616 cites W2003910176 @default.
• W4211132616 cites W2007248297 @default.
• W4211132616 cites W2009075135 @default.
• W4211132616 cites W2020627436 @default.
• W4211132616 cites W2024223938 @default.
• W4211132616 cites W2027407556 @default.
• W4211132616 cites W2028142668 @default.
• W4211132616 cites W2031694888 @default.
• W4211132616 cites W2038219325 @default.
• W4211132616 cites W2039247749 @default.
• W4211132616 cites W2039803772 @default.
• W4211132616 cites W2042000465 @default.
• W4211132616 cites W2042271989 @default.
• W4211132616 cites W204453894 @default.
• W4211132616 cites W2045328198 @default.
• W4211132616 cites W2047425497 @default.
• W4211132616 cites W2049733183 @default.
• W4211132616 cites W2051785964 @default.
• W4211132616 cites W2052344884 @default.
• W4211132616 cites W2054773248 @default.
• W4211132616 cites W2054818500 @default.
• W4211132616 cites W2054944069 @default.
• W4211132616 cites W2056042121 @default.
• W4211132616 cites W2057900646 @default.
• W4211132616 cites W2058390587 @default.
• W4211132616 cites W2059698989 @default.
• W4211132616 cites W2060248959 @default.
• W4211132616 cites W2060925223 @default.
• W4211132616 cites W2061560828 @default.
• W4211132616 cites W2065355061 @default.
• W4211132616 cites W2067830416 @default.
• W4211132616 cites W2068608642 @default.
• W4211132616 cites W2068775214 @default.
• W4211132616 cites W2073791781 @default.
• W4211132616 cites W2075926239 @default.
• W4211132616 cites W2076352568 @default.
• W4211132616 cites W2076621771 @default.
• W4211132616 cites W2077558850 @default.
• W4211132616 cites W2079742805 @default.
• W4211132616 cites W2082153983 @default.
• W4211132616 cites W2084595268 @default.
• W4211132616 cites W2087212202 @default.
• W4211132616 cites W2087863181 @default.
• W4211132616 cites W2088106923 @default.

• next