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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Nafazatrom (Bay g-6575), an antithrombotic and antimetastatic agent, inhibits 15-hydroxyprostaglandin dehydrogenase.

Nafazatrom (Bay g-6575) is a potent antithrombotic agent which has been suggested to stimulate prostacyclin (PGI2) release from the vascular wall. This study demonstrates that nafazatrom inhibits 15-hydroxyprostaglandin dehydrogenase (15-OH PGDH) of bovine lung and vascular wall. As 15-OH PGDH, the key prostaglandin (PG) catabolizing enzyme, inactivates PGI2 as well as PGE2 and PGF2 alpha, inhibition of this enzyme can result in increased levels of PGI2. Nafazatrom, in the micromolar range, inhibits the metabolism of PGs by 15-OH PGDH in a dose-dependent manner. The IC50 for inhibition of 15-OH PGDH was estimated to be 18.5 microM when [3H]PGF2 alpha was used as substrate. We also estimated nafazatrom-induced changes in PGI2 degradation by lung 15-OH PGDH using the more stable methyl ester (ME) of PGI2 (PGI2-ME) which resists spontaneous degradation. Nafazatrom also inhibited catabolism by 15-OH PGDH of [3H]PGI2-ME to [3H]6,15-diketo-PGF1 alpha ME. These results suggest that the inhibitory action of nafazatrom on 15-OH PGDH contributes to its antithrombotic effect by prolonging the biological half-life of PGI2.[1]


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