The Chemistry section is headed by Dr. Richard Cysyk, who works collarboratively with the FDA. Dr. Cysyk is studying the mechanism of action of Zebularine, with the goal of increasing bioavailability. Dr. Cysyk has found that Zebularine is metabolized by aldehyde oxidase. This pathway is thought to underlie the fluctuations in Zebularine blood levels seen in nonhuman primates. A manuscript is submitted.Dr. Cysyk has also studied the Hsp90 inhibitor geldanamycin and its analogs. The major limiting toxicity is hepatic. Dr. Cysyk has found that geldanamycins form irreversible complexes with glutathione, which may impact their activity and toxicity profile. A manuscript is submitted on this project. Dr. Cysyk also studies pharmacogenomics, using in vitro human liver cells.
| Cysyk, Richard L; Parker, Robert J; Barchi Jr, Joseph J et al. (2006) Reaction of geldanamycin and C17-substituted analogues with glutathione: product identifications and pharmacological implications. Chem Res Toxicol 19:376-81 |
| Klecker, Raymond W; Cysyk, Richard L; Collins, Jerry M (2006) Zebularine metabolism by aldehyde oxidase in hepatic cytosol from humans, monkeys, dogs, rats, and mice: influence of sex and inhibitors. Bioorg Med Chem 14:62-6 |
