Efforts in redesigning the antileukemic drug 6-thiopurine: decreasing toxic side effects while maintaining efficacy.

ABSTRACT: 6-Thiopurine (6TP) is a currently prescribed drug in the treatment of diseases ranging from Crohn's disease to acute lymphocytic leukemia. While its potent mode of action is through incorporation into DNA as a thiol mimic of deoxyguanosine, severe toxicities are associated with its administration which hinder the potential therapeutic application. We have previously reported in vitro that the oxidative metabolites of 6TP, specifically 6-thiouric acid (6TU, K _i 7 μM), are potent inhibitors of UDP-glucose dehydrogenase (UDPGDH), an enzyme that is responsible for the formation of UDP-glucuronic acid (UDPGA), an essential substrate that is used in detoxification processes in the liver. An in vivo investigation was undertaken to probe if 6TU inhibits UDPGDH in ra

SUBMITTER: Torres Hernandez AX 

PROVIDER: S-EPMC6350761 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature