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We have a drug. Its major metabolic pathway in the rat is hydration
We proved it's an enzymatic process. We tried several inhibitors.
1. a-Naphthaflavone (somebody used it as non-specific epoxide
hydrolase inhibitor) produce a maximum inhibition of 25%.
2. TOCP (specific carboxyesterase inhibitor): no inhibition
3. iso-OMPA (specific butyrylcholinesterase inhibitor): no
inhibition (inhibitory effect on its prototypic substrate was proved)
4. BW284c51 (specific acetylcholinesterase inhibitor): no
5. EDTA (inhibit PON1 which needs Ca2+ for its action): no
6. Triton X-100 (somebody used it as non-specific inhibitor of
carboxyesterase): dose-dependent and complete inhibition at 10 mM
Other characteristics of this responsible enzyme(s) in the rat:
1) not in the plasma
2) mainly soluble form
3) In intestinal S9, cytosol, M1 is the only metabolite. No
metabolite in microsome; Exhibits almost the same activity along
different segment of small intestine
4) in hepatic S9, cytosol, M1 is almost the only metabolite;
in microsome M1 and other hydroxylated metabolites are main metabolites.
Very appreciate any suggestion for elucidation of the enzyme(s).
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