15-DESMETHYL FK-506 AND 15,31-DESMETHYL FK-506 FROM HUMAN LIVER-MICROSOMES - ISOLATION, IDENTIFICATION (BY FAST-ATOM-BOMBARDMENT MASS-SPECTROMETRY AND NMR), AND EVALUATION OF IN-VITRO IMMUNOSUPPRESSIVE ACTIVITY

Authors
LHOEST GJJ MATON N LATINNE D LAURENT A VERBEECK RK
Citation
Gjj. Lhoest et al., 15-DESMETHYL FK-506 AND 15,31-DESMETHYL FK-506 FROM HUMAN LIVER-MICROSOMES - ISOLATION, IDENTIFICATION (BY FAST-ATOM-BOMBARDMENT MASS-SPECTROMETRY AND NMR), AND EVALUATION OF IN-VITRO IMMUNOSUPPRESSIVE ACTIVITY, Clinical chemistry, 40(5), 1994, pp. 740-744
Citations number
19
Categorie Soggetti
Chemistry Medicinal
Journal title
Clinical chemistry → ACNP
ISSN journal
00099147
Volume
40
Issue
5
Year of publication
1994
Pages
740 - 744
Database
ISI
SICI code
0009-9147(1994)40:5<740:1FA1FF>2.0.ZU;2-9
Abstract
15-Desmethyl FK-506 and 15,31-desmethyl FK-506 metabolites extracted f rom incubated human liver microsomes were separated by normal and reve rsed-phase HPLC. The metabolites were identified by fast atom bombardm ent/mass spectrometry and nuclear magnetic resonance spectroscopy. The in vitro 50% inhibitory concentration, tested against bidirectional m ixed lymphocyte reactions, was 325 mg/L for 15,31-desmethyl FK-506 and 4 mg/L for 15-desmethyl FK-506, indicating that these products of FK- 506 demethylation retain in vitro immunosuppressive activity.