Bioactivation of 6,7-dimethyl-2,4-di-1-pyrrolidinyl-7H-pyrrolo[2,3-d]pyrimidine (U-89843) to reactive intermediates that bind covalently to macromolecules and produce genotoxicity.

@article{Zhao1996BioactivationO6,
  title={Bioactivation of 6,7-dimethyl-2,4-di-1-pyrrolidinyl-7H-pyrrolo[2,3-d]pyrimidine (U-89843) to reactive intermediates that bind covalently to macromolecules and produce genotoxicity.},
  author={Z Y Zhao and Kenneth Koeplinger and G. E. Padbury and M J Hauer and Gordon Bundy and Lee S. Banitt and Theresa M. Schwartz and David C. Zimmermann and Philip R. Harbach and J. K. Mayo and C. S. Aaron},
  journal={Chemical research in toxicology},
  year={1996},
  volume={9 8},
  pages={
          1230-9
        }
}
U-89843 is a novel pyrrolo[2,3-d]pyrimidine antioxidant with prophylactic activity in animal models of lung inflammation. During preclinical safety evaluation, U-89843 was found to give a positive response in the in vitro unscheduled DNA synthesis (UDS) assay, an assay which measures DNA repair following chemically-induced DNA damage in metabolically competent rat hepatocytes. Incubation of [14C]U-89843 with liver microsomes resulted in covalent binding of radioactive material to macromolecules… Expand
9 Citations
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The results suggest that the effect of serum protein should be considered when comparing serum-free in vitro UDS and in vivo UDS results for highly serum protein bound compounds. Expand
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