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- W1991444357 abstract "Macrolide immunosuppressive drugs such as tacrolimus (FK506) and sirolimus (rapamycin) are compounds largely used in modern immunosuppressive therapy and considered as powerful immunosuppressive agents. Some of these molecules are still under clinical development as, for example, SDZ-RAD (40-O-(2-hydroxyethyl)rapamycin), an immunosuppressive drug closely related to rapamycin. SDZ-RAD has a molecular mass of 957.57 Da (C53H83NO14) and shares the same common intracellular receptor as tacrolimus, the FK-506 binding protein (FKBP-12). SDZ-RAD exerts its pharmacological effect by binding to a different effector protein, inhibits the S6p 70-kinase and interrupts a different signal transduction pathway than tacrolimus. Both SDZ-RAD and rapamycin are metabolized mainly by the cytochrome P-450 3A4-dependent mixed function oxygenase enzyme system to hydroxylated and demethylated metabolites. We describe here the isolation from pig liver microsomes of a novel SDZ-RAD metabolite identified by electrospray tandam mass spectrometry as a new SDZ-RAD 17,18,19,20,21,22-tris-epoxide metabolite. The in vitro immunosuppressive activity as measured by the mixed lymphocyte reaction is more or less comparable to that of SDZ-RAD, although its pharmacological mode of action may be different from that classically described for rapamycin." @default.
- W1991444357 created "2016-06-24" @default.
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- W1991444357 date "2000-03-01" @default.
- W1991444357 modified "2023-09-27" @default.
- W1991444357 title "Isolation from pig liver microsomes, identification by tandem mass spectrometry andin vitro immunosuppressive activity of an SDZ-RAD 17,18,19,20,21,22-tris-epoxide" @default.
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- W1991444357 doi "https://doi.org/10.1002/(sici)1096-9888(200003)35:3<454::aid-jms959>3.0.co;2-k" @default.
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