Matches in SemOpenAlex for { <https://semopenalex.org/work/W2780291271> ?p ?o ?g. }
Showing items 1 to 94 of
94
with 100 items per page.
- W2780291271 abstract "6-Thiopurine (6TP) is an actively prescribed drug in the treatment of various diseases ranging from Crohn's disease and other inflammatory diseases to acute lymphocytic leukemia and non-Hodgkin's leukemia. While 6TP has beneficial therapeutic uses, severe toxicities are also reported with its use, such as jaundice and liver toxicity. While numerous investigations into the mode in which toxicity originates has been undertaken. None have investigated the effects of inhibition towards UDP-Glucose Dehydrogenase (UDPGDH), an oxidative enzyme responsible for UDP-glucuronic acid (UDPGA) formation or UDP-Glucuronosyl transferase (UGT1A1), which is responsible for the conjugation of bilirubin with UDPGA for excretion. Failure to excrete bilirubin leads to jaundice and liver toxicity. We proposed that either 6TP or its primary oxidative excretion metabolites inhibit one or both of these enzymes, resulting in the observed toxicity from 6TP administration. Inhibition analysis of these purines revealed that 6-thiopurine has weak to no inhibition towards UDPGDH with a Ki of 288 μM with regard to varying UDP-glucose, but 6-thiouric (primary end metabolite, fully oxidized at carbon 2 and 8, and highly retained by the body) has a near six-fold increased inhibition towards UDPGDH with a Ki of 7 μM. Inhibition was also observed by 6-thioxanthine (oxidized at carbon 2) and 8-OH-6TP with Ki values of 54 and 14 μM, respectively. Neither 6-thiopurine or its excretion metabolites were shown to inhibit UGT1A1. Our results show that the C2 and C8 positions of 6TP are pivotal in said inhibition towards UDPGDH and have no effect upon UGT1A1, and that blocking C8 could lead to new analogs with reduced, if not eliminated jaundice and liver toxicities." @default.
- W2780291271 created "2018-01-05" @default.
- W2780291271 creator A5003464835 @default.
- W2780291271 creator A5030867486 @default.
- W2780291271 creator A5049845414 @default.
- W2780291271 creator A5070387497 @default.
- W2780291271 date "2018-03-01" @default.
- W2780291271 modified "2023-09-24" @default.
- W2780291271 title "Inhibition of UDP-glucose dehydrogenase by 6-thiopurine and its oxidative metabolites: Possible mechanism for its interaction within the bilirubin excretion pathway and 6TP associated liver toxicity" @default.
- W2780291271 cites W1213222761 @default.
- W2780291271 cites W1911868485 @default.
- W2780291271 cites W1966795952 @default.
- W2780291271 cites W1987509648 @default.
- W2780291271 cites W1992033907 @default.
- W2780291271 cites W2009970359 @default.
- W2780291271 cites W2024221500 @default.
- W2780291271 cites W2027783682 @default.
- W2780291271 cites W2051907464 @default.
- W2780291271 cites W2065559890 @default.
- W2780291271 cites W2070005495 @default.
- W2780291271 cites W2073082612 @default.
- W2780291271 cites W2089190709 @default.
- W2780291271 cites W2098429461 @default.
- W2780291271 cites W2100414335 @default.
- W2780291271 cites W2104737185 @default.
- W2780291271 cites W2114771739 @default.
- W2780291271 cites W2119515450 @default.
- W2780291271 cites W2139540775 @default.
- W2780291271 cites W2188997920 @default.
- W2780291271 cites W2318554776 @default.
- W2780291271 cites W2395022933 @default.
- W2780291271 cites W2397408405 @default.
- W2780291271 cites W2548090658 @default.
- W2780291271 cites W2566102255 @default.
- W2780291271 doi "https://doi.org/10.1016/j.jpba.2017.12.058" @default.
- W2780291271 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29324279" @default.
- W2780291271 hasPublicationYear "2018" @default.
- W2780291271 type Work @default.
- W2780291271 sameAs 2780291271 @default.
- W2780291271 citedByCount "4" @default.
- W2780291271 countsByYear W27802912712019 @default.
- W2780291271 countsByYear W27802912712021 @default.
- W2780291271 crossrefType "journal-article" @default.
- W2780291271 hasAuthorship W2780291271A5003464835 @default.
- W2780291271 hasAuthorship W2780291271A5030867486 @default.
- W2780291271 hasAuthorship W2780291271A5049845414 @default.
- W2780291271 hasAuthorship W2780291271A5070387497 @default.
- W2780291271 hasConcept C10146269 @default.
- W2780291271 hasConcept C126322002 @default.
- W2780291271 hasConcept C178790620 @default.
- W2780291271 hasConcept C185592680 @default.
- W2780291271 hasConcept C2777477808 @default.
- W2780291271 hasConcept C2777513400 @default.
- W2780291271 hasConcept C2778260677 @default.
- W2780291271 hasConcept C2779134260 @default.
- W2780291271 hasConcept C29730261 @default.
- W2780291271 hasConcept C55493867 @default.
- W2780291271 hasConcept C70917649 @default.
- W2780291271 hasConcept C71924100 @default.
- W2780291271 hasConcept C86803240 @default.
- W2780291271 hasConcept C98274493 @default.
- W2780291271 hasConceptScore W2780291271C10146269 @default.
- W2780291271 hasConceptScore W2780291271C126322002 @default.
- W2780291271 hasConceptScore W2780291271C178790620 @default.
- W2780291271 hasConceptScore W2780291271C185592680 @default.
- W2780291271 hasConceptScore W2780291271C2777477808 @default.
- W2780291271 hasConceptScore W2780291271C2777513400 @default.
- W2780291271 hasConceptScore W2780291271C2778260677 @default.
- W2780291271 hasConceptScore W2780291271C2779134260 @default.
- W2780291271 hasConceptScore W2780291271C29730261 @default.
- W2780291271 hasConceptScore W2780291271C55493867 @default.
- W2780291271 hasConceptScore W2780291271C70917649 @default.
- W2780291271 hasConceptScore W2780291271C71924100 @default.
- W2780291271 hasConceptScore W2780291271C86803240 @default.
- W2780291271 hasConceptScore W2780291271C98274493 @default.
- W2780291271 hasFunder F4320310106 @default.
- W2780291271 hasLocation W27802912711 @default.
- W2780291271 hasLocation W27802912712 @default.
- W2780291271 hasOpenAccess W2780291271 @default.
- W2780291271 hasPrimaryLocation W27802912711 @default.
- W2780291271 hasRelatedWork W1979789677 @default.
- W2780291271 hasRelatedWork W1995226647 @default.
- W2780291271 hasRelatedWork W2023487034 @default.
- W2780291271 hasRelatedWork W2075012981 @default.
- W2780291271 hasRelatedWork W2112727823 @default.
- W2780291271 hasRelatedWork W2136402305 @default.
- W2780291271 hasRelatedWork W2336887693 @default.
- W2780291271 hasRelatedWork W2460410212 @default.
- W2780291271 hasRelatedWork W2886148610 @default.
- W2780291271 hasRelatedWork W2785926487 @default.
- W2780291271 isParatext "false" @default.
- W2780291271 isRetracted "false" @default.
- W2780291271 magId "2780291271" @default.
- W2780291271 workType "article" @default.