FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2023896314> ?p ?o ?g. }

• W2023896314 endingPage "271" @default.
• W2023896314 startingPage "261" @default.
• W2023896314 abstract "2-Amino-6-chloro-1-deazapurine is of interest as a purine analog with demonstrated in vivo activity against mouse leukemia L1210. That the active form of this agent is a nucleotide and that the nucleotide is formed by the action of hypoxanthine (guanine) phosphoribosyltransferase were shown by the facts that (a) L1210 cells deficient in hypoxanthine phosphoribosyltransferase were insensitive to the analog; (b) hypoxanthine, but not adenine, prevented the formation of the analog nucleotide by enzyme preparations containing activities of both hypoxanthine and adenine phosphoribosyltransferases; and (c) the cytotoxicity of the analog was prevented by hypoxanthine. The ribonucleoside of this analog was not toxic to cell cultures and hence is not phosphorylated or cleaved to the base. In intact HEp-2 cells and L1210 cells, the analog was metabolized to the nucleoside 5′-phosphate which accumulated to concentrations as high as 1000 nmoles/109 cells; no di- or triphosphates were detected. In HEp-2 cells, the analog reduced the pools of purine nucleotides with some accumulation of IMP. The toxicity of minimal inhibitory concentrations of the analog to HEp-2 cells could be prevented or reversed by 4(5)-amino-5(4)-imidazolecarboxamide (AIC); the toxicity of higher concentrations could be prevented or reversed by a combination of adenine and guanosine but not by AIC. The analog inhibited the incorporation of formate into purine nucleotides and into macromolecules at concentrations that had no effect on utilization of hypoxanthine; at higher concentrations the incorporation of hypoxanthine was inhibited. Low concentrations also inhibited the utilization of uridine and thymidine. The incorporation of hypoxanthine and AIC into guanine nucleotides, but not adenine nucleotides, was inhibited. These results indicate two sites of inhibition of the biosynthesis of purine nucleotides, the more sensitive one being on an early step of the pathway and the less sensitive one on the IMP-GMP conversion. That the blockade of de novo synthesis probably was at the site of feedback inhibition was indicated by the fact that the analog inhibited the accumulation of formylglycinamide ribonucleotide in azaserine-treated cells but did not inhibited the synthesis of 5′-phosphoribosyl 1-pyrophosphate. Comparative studies were performed with the related analog, 2-amino-6-chloropurine, which has been reported to produce a similar dual blockade of the purine pathway. This purine was less toxic than its 1-deaza analog; it produced a modest decrease in adenine nucleotides but increased pools of guanine nucleotides. IMP dehydrogenase from L1210 cells was not inhibited by the nucleotides of 2-amino-6-chloropurine or 2-amino-6-chloro-1-deazapurine at 1 mM comcentrations. The nucleotide of 2-amino-6-chloropurine was dechlorinated by AMP deaminase; the apparent Km was about the same as that of AMP and the Vmax was 21% that of AMP. The nucleotide of 2-amino-6-chloro-1-deazapurine was not a substrate. Conversion of the nucleotide of 2-amino-6-chloropurine to GMP by the action of AMP deaminase explains both the lower toxicity of 2-amino-6-chloropurine as compared to its 1-deaza analog and its capacity to increase pools of guanine nucleotides. Thus, of the two compounds the 1-deaza analog may be the more interesting as an antitumor agent because of the greater metabolic stability of its nucleotide." @default.
• W2023896314 created "2016-06-24" @default.
• W2023896314 creator A5010951243 @default.
• W2023896314 creator A5026062306 @default.
• W2023896314 creator A5033699639 @default.
• W2023896314 creator A5065269848 @default.
• W2023896314 creator A5091391388 @default.
• W2023896314 date "1984-01-01" @default.
• W2023896314 modified "2023-09-27" @default.
• W2023896314 title "Mode of action of 2-amino-6-chloro-1-deazapurine" @default.
• W2023896314 cites W1131690488 @default.
• W2023896314 cites W1577473555 @default.
• W2023896314 cites W1983409590 @default.
• W2023896314 cites W2006322990 @default.
• W2023896314 cites W2017471354 @default.
• W2023896314 cites W2026788522 @default.
• W2023896314 cites W2033246082 @default.
• W2023896314 cites W2035440361 @default.
• W2023896314 cites W2044484957 @default.
• W2023896314 cites W2045340750 @default.
• W2023896314 cites W2078363332 @default.
• W2023896314 cites W2155059327 @default.
• W2023896314 cites W2263784374 @default.
• W2023896314 cites W2280449939 @default.
• W2023896314 cites W2327158115 @default.
• W2023896314 cites W4233934059 @default.
• W2023896314 cites W4249385166 @default.
• W2023896314 doi "https://doi.org/10.1016/0006-2952(84)90484-2" @default.
• W2023896314 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/6142712" @default.
• W2023896314 hasPublicationYear "1984" @default.
• W2023896314 type Work @default.
• W2023896314 sameAs 2023896314 @default.
• W2023896314 citedByCount "9" @default.
• W2023896314 countsByYear W20238963142018 @default.
• W2023896314 countsByYear W20238963142021 @default.
• W2023896314 crossrefType "journal-article" @default.
• W2023896314 hasAuthorship W2023896314A5010951243 @default.
• W2023896314 hasAuthorship W2023896314A5026062306 @default.
• W2023896314 hasAuthorship W2023896314A5033699639 @default.
• W2023896314 hasAuthorship W2023896314A5065269848 @default.
• W2023896314 hasAuthorship W2023896314A5091391388 @default.
• W2023896314 hasConcept C104317684 @default.
• W2023896314 hasConcept C143065580 @default.
• W2023896314 hasConcept C169586020 @default.
• W2023896314 hasConcept C181199279 @default.
• W2023896314 hasConcept C185592680 @default.
• W2023896314 hasConcept C2776476023 @default.
• W2023896314 hasConcept C2776543447 @default.
• W2023896314 hasConcept C2776844798 @default.
• W2023896314 hasConcept C2776991684 @default.
• W2023896314 hasConcept C2777610669 @default.
• W2023896314 hasConcept C2777991568 @default.
• W2023896314 hasConcept C2777995097 @default.
• W2023896314 hasConcept C2778301229 @default.
• W2023896314 hasConcept C2781116151 @default.
• W2023896314 hasConcept C2909697302 @default.
• W2023896314 hasConcept C40507961 @default.
• W2023896314 hasConcept C512185932 @default.
• W2023896314 hasConcept C55493867 @default.
• W2023896314 hasConcept C67705224 @default.
• W2023896314 hasConcept C71240020 @default.
• W2023896314 hasConcept C71615608 @default.
• W2023896314 hasConcept C78179603 @default.
• W2023896314 hasConceptScore W2023896314C104317684 @default.
• W2023896314 hasConceptScore W2023896314C143065580 @default.
• W2023896314 hasConceptScore W2023896314C169586020 @default.
• W2023896314 hasConceptScore W2023896314C181199279 @default.
• W2023896314 hasConceptScore W2023896314C185592680 @default.
• W2023896314 hasConceptScore W2023896314C2776476023 @default.
• W2023896314 hasConceptScore W2023896314C2776543447 @default.
• W2023896314 hasConceptScore W2023896314C2776844798 @default.
• W2023896314 hasConceptScore W2023896314C2776991684 @default.
• W2023896314 hasConceptScore W2023896314C2777610669 @default.
• W2023896314 hasConceptScore W2023896314C2777991568 @default.
• W2023896314 hasConceptScore W2023896314C2777995097 @default.
• W2023896314 hasConceptScore W2023896314C2778301229 @default.
• W2023896314 hasConceptScore W2023896314C2781116151 @default.
• W2023896314 hasConceptScore W2023896314C2909697302 @default.
• W2023896314 hasConceptScore W2023896314C40507961 @default.
• W2023896314 hasConceptScore W2023896314C512185932 @default.
• W2023896314 hasConceptScore W2023896314C55493867 @default.
• W2023896314 hasConceptScore W2023896314C67705224 @default.
• W2023896314 hasConceptScore W2023896314C71240020 @default.
• W2023896314 hasConceptScore W2023896314C71615608 @default.
• W2023896314 hasConceptScore W2023896314C78179603 @default.
• W2023896314 hasIssue "2" @default.
• W2023896314 hasLocation W20238963141 @default.
• W2023896314 hasLocation W20238963142 @default.
• W2023896314 hasOpenAccess W2023896314 @default.
• W2023896314 hasPrimaryLocation W20238963141 @default.
• W2023896314 hasRelatedWork W1525746198 @default.
• W2023896314 hasRelatedWork W1630992622 @default.
• W2023896314 hasRelatedWork W1759730928 @default.
• W2023896314 hasRelatedWork W1985654998 @default.
• W2023896314 hasRelatedWork W2013157260 @default.
• W2023896314 hasRelatedWork W2023033821 @default.
• W2023896314 hasRelatedWork W2023896314 @default.
• W2023896314 hasRelatedWork W2034664886 @default.

• next