Pharmacogenomics of Immunosuppressants

Picard, Nicolas; Marquet, Pierre

doi:10.1002/9781119959601.ch6

Cited by 1 publication

(1 citation statement)

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“…According to the published reports, MPA is mainly metabolized to its inactive MPA‐phenyl‐glucuronide (MPAG) by several members of the UDP glucuronosyltransferase 1A family in which UGT1A9 (highly expressed in human kidney and liver) and UGT1A8 (exclusively expressed in intestinal cells) are the major enzymes. MPA is also metabolized to a minor acyl‐MPA‐glucuronide (acMPAG) by UGT2B7 and UGT1A8 (Picard and Marquet, ; Shipkova et al, ). In contrast to MPAG, acMPAG inhibits inosine‐monophosphate dehydrogenase activity with the same uncompetitive mechanism as MPA (Klepacki et al, ; Wolff et al, ).…”

Section: Resultsmentioning

confidence: 99%

Identifying the differences in mechanisms of mycophenolic acid controlling fucose content of glycoproteins expressed in different CHO cell lines

Zhang

Tsang

Markely

et al. 2016

Biotech & Bioengineering

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In the biopharmaceutical industry, glycosylation is a critical quality attribute that can modulate the efficacy of a therapeutic glycoprotein. Obtaining a consistent glycoform profile is desired because molecular function can be defined by its carbohydrate structures. Specifically, the fucose content of oligosaccharides in glycoproteins is one of the most important attributes that can significantly affect antibody-dependent cellular cytotoxicity (ADCC) activity. It is therefore important to understand the fucosylation pathway and be able to control fucosylation at the desired level to match predecessor materials in late stage and biosimilar programs. Several strategies were explored in this study and mycophenolic acid (MPA) was able to finely modulate the fucose content with the least undesired side effects. However, the response was significantly different between CHO cell lines of different lineages. Further experiments were then performed for a deeper understanding of the mechanism of fucosylation in different CHO cell lines. Results indicated that changes in the intracellular nucleotide involved in fucosylation pathway after MPA treatment are the main cause of the differences in fucosylation level response in different CHO cell lines. Differences in MPA metabolism in the various CHO cell lines directly resulted in different levels of afucosylation measured in antibodies produced by the CHO cell lines. Biotechnol. Bioeng. 2016;113: 2367-2376. © 2016 Wiley Periodicals, Inc.

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Section: Resultsmentioning

confidence: 99%