Markus Zollinger

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Immunosuppressant drugs such as cyclosporin have allowed widespread organ transplantation, but their utility remains limited by toxicities, and they are ineffective in chronic management of autoimmune diseases such as multiple sclerosis. In contrast, the immune modulating drug FTY720 is efficacious in a variety of transplant and autoimmune models without(More)
Imatinib mesylate (GLEEVEC, GLIVEC, formerly STI571) has demonstrated unprecedented efficacy as first-line therapy for treatment for all phases of chronic myelogenous leukemia and metastatic and unresectable malignant gastrointestinal stromal tumors. Disposition and biotransformation of imatinib were studied in four male healthy volunteers after a single(More)
The subcellular localization and maturation of starch phosphorylase (EC was studied in developing potato tubers. The enzyme is localized inside the stroma of amyloplasts in young tubers, whereas in mature tubers it is found within the cytoplasm in the immediate vicinity of the plastids. A phosphorylase cDNA clone was isolated and used in RNA gel(More)
Fingolimod (FTY720, Gilenya, 2-amino-2-[2-(4-octylphenyl)ethyl]-1,3-propanediol) is a novel drug recently approved in the United States for the oral treatment of relapsing multiple sclerosis. The compound is eliminated predominantly by ω-hydroxylation, followed by further oxidation. The ω-hydroxylation was the major metabolic pathway in human liver(More)
Fingolimod [(FTY720), Gilenya; 2-amino-2-[2-(4-octylphenyl)ethyl]-1,3-propanediol], a new drug for the treatment of relapsing multiple sclerosis, acts through its phosphate metabolite, which modulates sphingosine 1-phosphate receptors. This represents a novel mechanism of action. In the present work, the absorption and disposition of (14)C-labeled(More)
Biotransformation pathways and the potential for drug-drug interactions of the orally active antifungal terbinafine were characterized using human liver microsomes and recombinant human cytochrome P-450s (CYPs). The terbinafine metabolites represented four major pathways: 1) N-demethylation, 2) deamination, 3) alkyl side chain oxidation, and 4) dihydrodiol(More)
The absorption, distribution, metabolism, and excretion of the hedgehog pathway inhibitor sonidegib (LDE225) were determined in healthy male subjects. Six subjects received a single oral dose of 800 mg 14C-sonidegib (74 kBq, 2.0 µCi) under fasting conditions. Blood, plasma, urine, and fecal samples were collected predose, postdose in-house (days 1–22), and(More)
Neutral endopeptidase (EC is an integral membrane protein found in the plasma membrane of many cell types. The cDNA coding for the complete primary structure of neutral endopeptidase has recently been cloned and sequenced (Devault, A. Lazure, C., Nault, C., Le Moual, H., Seidah, N. G., Chretien, M., Kahn, P., Powell, J., Mallet, J., Beaumont, A.,(More)
The ergot alkaloid CQA 206-291 (CQA) was converted by human liver microsomes (n = 16) almost exclusively to the N-deethylated metabolite (I), as identified by the on-line coupling of liquid chromatography and mass spectroscopy. Metabolite I formation exhibited monophasic and linear enzyme kinetics (2.9-300 microM), and a 5.6-fold interindividual variability(More)
The structure of pro-opiomelanocortin (POMC) can be divided into three main domains: an NH2-terminal domain formed by the NH2-terminal glycopeptide and the joining peptide, a central domain corresponding to the adrenocorticotropin sequences and a COOH-terminal domain containing the beta-lipotropin sequences. Expression of POMC in neuroendocrine cell lines(More)