Cytotoxicity and antitumor activity of carzelesin, a prodrug cyclopropylpyrroloindole analogue.
- L. Li, T. Dekoning, M. Prairie
- Biology, ChemistryCancer Research
- 15 September 1992
The results, collectively, suggest that carzelesin is absorbed and distributed well and that it was therapeutically more efficacious against mouse L1210 leukemia than was U-76074 or adozelesin (U-73975), another cyclopropylpyrroloindole analogue which is currently in phase I clinical trials.
Pyrrolopyrimidines: novel brain-penetrating antioxidants with neuroprotective activity in brain injury and ischemia models.
- E. Hall, P. K. Andrus, G. Bundy
- BiologyJournal of Pharmacology and Experimental…
- 1 May 1997
The results suggest that antioxidant compounds with improved brain parenchymal penetration are better able to limit certain types of ischemic brain damage than those which are localized in the cerebral microvasculature.
Increased lipophilicity and subsequent cell partitioning decrease passive transcellular diffusion of novel, highly lipophilic antioxidants.
- G. Sawada, C. Barsuhn, Thomas J. Raub
- Biology, ChemistryJournal of Pharmacology and Experimental…
- 1 March 1999
These in vitro cell monolayer models do not adequately mimic the in vivo situation by underestimating in vivo bioavailability of highly lipophilic compounds unless acceptors, such as serum proteins, are added to the receiving buffer.
Factors impacting the delivery of therapeutic levels of pyrone-based HIV protease inhibitors.
- G. Padbury, G. L. Zipp, S. Thaisrivongs
- BiologyPharmaceutical biotechnology
Chemical reactivities of bleomycin.
- G. Padbury, S. Sligar
- Chemistry, BiologyJournal of Biological Chemistry
- 5 July 1985
Ferric bleomycin catalyzed reduction of 10-hydroperoxy-8,12-octadecadienoic acid: evidence for homolytic O-O bond scission.
- G. Padbury, S. Sligar, R. Labeque, L. Marnett
- 4 October 1988
The results of this investigation indicate that ferric bleomycin catalyzes the homolytic cleavage of the O-O bond of 1 almost exclusively while supporting various oxidative reactions.
Equilibrium distribution of HIV antiviral drugs into human peripheral blood mononuclear cells (PBMC) is controlled by free drug concentration in the extracellular medium.
- K. Koeplinger, Thomas J. Raub, G. Padbury, Z. Zhao
- Biology, MedicineJournal of Pharmaceutical and Biomedical Analysis
- 1 March 1999
Species-dependent enantioselective pharmacokinetics of PNU-103017, a pyrone HIV protease inhibitor.
- W. Zhong, M. Williams, M. Borin, G. Padbury
- Chemistry, BiologyChirality
The enantiomeric ratio remained unchanged after multiple dose administration in the rat, dog, and human although enzyme induction and increased plasma clearance were observed for both enantiomers.
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.
- Z. Zhao, K. Koeplinger, C. Aaron
- Chemistry, BiologyChemical Research in Toxicology
- 27 November 1996
Observations suggest that the positive in vitro UDS results of U-89843 are mediated by the bioactivation of the novel pyrrolo[2,3-d]pyrimidine antioxidant, leading to reactive electrophilic intermediates derived from the (hydroxymethyl)pyrrole metabolite U-97924.
The Time to Move Cytochrome P450 Induction into Mainstream Pharmacology Is Long Overdue
- Dennis A. Smith, M. Dickins, K. Youdim
- Biology, MedicineDrug Metabolism And Disposition
- 1 April 2007
The understanding of the processes of induction of human drug-metabolizing enzymes has advanced considerably over the past decade. If we concentrate on CYP3A4, the most abundant form of cytochrome…