FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2013553237> ?p ?o ?g. }

• W2013553237 endingPage "398" @default.
• W2013553237 startingPage "391" @default.
• W2013553237 abstract "N-[5-[N-(3,4-Dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N- methylamino]-2-thenoyl]-L-glutamic acid (ZD1694) is a folate-based thymidylate synthase (TS; EC 2.1.1.45) inhibitor. Metabolism to higher chain length polyglutamates is essential for its optimal cytotoxic effect. A ZD1694-resistant (300-fold) human ileocecal carcinoma cell line (HCT-8/DW2) was developed, and its mechanism of resistance was evaluated. TS activities in situ and TS protein levels in the HCT-8 parental line and HCT-8/DW2 were similar (168 +/- 47 vs 137 +/- 25 pmol/hr/10(6) cells and 2.05 +/- 0.28 vs 2.07 +/- 0.19 pmol/mg protein, respectively). The IC50 values of ZD1694 for TS inhibition in cell-free extracts were similar in both lines, but the IC50 of ZD1694 for TS inhibition in situ in HCT-8/DW2 cells was 27- and 268-fold higher than that in HCT-8 cells at 0 and 24 hr, respectively, after a 2-hr drug exposure. Folylpolyglutamate synthetase (FPGS; EC6.3.2.17) activity was significantly lower in resistant HCT-8/DW2 cells as compared with parental HCT-8 cells (88 +/- 40 vs 1065 +/- 438 pmol/hr/mg protein when ZD1694 was used as substrate). The combined endogenous pool of methylenetetrahydrofolate and tetrahydrofolate in HCT-8/DW2 cells was also decreased. In addition, HCT-8/DW2 cells accumulated lower levels of methotrexate (MTX) in a 2-hr period, although the initial velocity of MTX transport was similar to that in parental HCT-8 cells. The lower level of FPGS activity and the lower level of (anti)folate accumulation in HCT-8/DW2 correlated with drug resistance and with the higher IC50 of ZD1694 for in situ TS inhibition. In addition, drug resistance was also correlated with the rapid recovery of in situ TS activity after drug treatment. In brief, in this highly ZD1694-resistant HCT-8 cell line, resistance is associated with decreased FPGS activity, which, in turn, affects the metabolism of ZD1694 and consequently the extent and duration of in situ TS inhibition by the drug." @default.
• W2013553237 created "2016-06-24" @default.
• W2013553237 creator A5028467039 @default.
• W2013553237 creator A5045095134 @default.
• W2013553237 creator A5047847395 @default.
• W2013553237 creator A5076225093 @default.
• W2013553237 creator A5091214681 @default.
• W2013553237 date "1995-07-01" @default.
• W2013553237 modified "2023-10-17" @default.
• W2013553237 title "Mechanisms of resistance to N-[5-[N-(3, 4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N-methylamino]-2-thenoyl]-L-glutamic acid (ZD1694), a folate-based thymidylate synthase inhibitor, in the HCT-8 human ileocecal adenocarcinoma cell line" @default.
• W2013553237 cites W1522337629 @default.
• W2013553237 cites W1589281120 @default.
• W2013553237 cites W1600598432 @default.
• W2013553237 cites W178877402 @default.
• W2013553237 cites W1830995821 @default.
• W2013553237 cites W1985319406 @default.
• W2013553237 cites W2024756387 @default.
• W2013553237 cites W2060333964 @default.
• W2013553237 cites W2076892293 @default.
• W2013553237 cites W2079752673 @default.
• W2013553237 cites W2109689528 @default.
• W2013553237 cites W2115231119 @default.
• W2013553237 cites W2149795002 @default.
• W2013553237 cites W2157595631 @default.
• W2013553237 doi "https://doi.org/10.1016/0006-2952(95)00135-m" @default.
• W2013553237 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/7646540" @default.
• W2013553237 hasPublicationYear "1995" @default.
• W2013553237 type Work @default.
• W2013553237 sameAs 2013553237 @default.
• W2013553237 citedByCount "36" @default.
• W2013553237 countsByYear W20135532372012 @default.
• W2013553237 countsByYear W20135532372015 @default.
• W2013553237 countsByYear W20135532372016 @default.
• W2013553237 crossrefType "journal-article" @default.
• W2013553237 hasAuthorship W2013553237A5028467039 @default.
• W2013553237 hasAuthorship W2013553237A5045095134 @default.
• W2013553237 hasAuthorship W2013553237A5047847395 @default.
• W2013553237 hasAuthorship W2013553237A5076225093 @default.
• W2013553237 hasAuthorship W2013553237A5091214681 @default.
• W2013553237 hasConcept C123321153 @default.
• W2013553237 hasConcept C126322002 @default.
• W2013553237 hasConcept C153911025 @default.
• W2013553237 hasConcept C181199279 @default.
• W2013553237 hasConcept C202751555 @default.
• W2013553237 hasConcept C203014093 @default.
• W2013553237 hasConcept C2776694085 @default.
• W2013553237 hasConcept C2776980637 @default.
• W2013553237 hasConcept C2777752497 @default.
• W2013553237 hasConcept C2778397455 @default.
• W2013553237 hasConcept C2780456651 @default.
• W2013553237 hasConcept C2781059491 @default.
• W2013553237 hasConcept C2781382166 @default.
• W2013553237 hasConcept C54355233 @default.
• W2013553237 hasConcept C55493867 @default.
• W2013553237 hasConcept C71924100 @default.
• W2013553237 hasConcept C81885089 @default.
• W2013553237 hasConcept C86803240 @default.
• W2013553237 hasConceptScore W2013553237C123321153 @default.
• W2013553237 hasConceptScore W2013553237C126322002 @default.
• W2013553237 hasConceptScore W2013553237C153911025 @default.
• W2013553237 hasConceptScore W2013553237C181199279 @default.
• W2013553237 hasConceptScore W2013553237C202751555 @default.
• W2013553237 hasConceptScore W2013553237C203014093 @default.
• W2013553237 hasConceptScore W2013553237C2776694085 @default.
• W2013553237 hasConceptScore W2013553237C2776980637 @default.
• W2013553237 hasConceptScore W2013553237C2777752497 @default.
• W2013553237 hasConceptScore W2013553237C2778397455 @default.
• W2013553237 hasConceptScore W2013553237C2780456651 @default.
• W2013553237 hasConceptScore W2013553237C2781059491 @default.
• W2013553237 hasConceptScore W2013553237C2781382166 @default.
• W2013553237 hasConceptScore W2013553237C54355233 @default.
• W2013553237 hasConceptScore W2013553237C55493867 @default.
• W2013553237 hasConceptScore W2013553237C71924100 @default.
• W2013553237 hasConceptScore W2013553237C81885089 @default.
• W2013553237 hasConceptScore W2013553237C86803240 @default.
• W2013553237 hasIssue "3" @default.
• W2013553237 hasLocation W20135532371 @default.
• W2013553237 hasLocation W20135532372 @default.
• W2013553237 hasOpenAccess W2013553237 @default.
• W2013553237 hasPrimaryLocation W20135532371 @default.
• W2013553237 hasRelatedWork W1966633783 @default.
• W2013553237 hasRelatedWork W2012859679 @default.
• W2013553237 hasRelatedWork W2015027939 @default.
• W2013553237 hasRelatedWork W2114000036 @default.
• W2013553237 hasRelatedWork W2134043283 @default.
• W2013553237 hasRelatedWork W2312586824 @default.
• W2013553237 hasRelatedWork W2332944239 @default.
• W2013553237 hasRelatedWork W2415964030 @default.
• W2013553237 hasRelatedWork W3208807108 @default.
• W2013553237 hasRelatedWork W2277199037 @default.
• W2013553237 hasVolume "50" @default.
• W2013553237 isParatext "false" @default.
• W2013553237 isRetracted "false" @default.
• W2013553237 magId "2013553237" @default.
• W2013553237 workType "article" @default.