In vitro characterization of the biotransformation of thiocoraline, a novel marine anti-cancer drug

Esther F A Brandon; Rolf Sparidans; Irma Meijerman; Ignasio Manzanares; Jos H. Beijnen; Jan H M Schellens

doi:10.1023/B:DRUG.0000026250.34645.7f

In vitro characterization of the biotransformation of thiocoraline, a novel marine anti-cancer drug

Esther F A Brandon^*, Rolf Sparidans, Irma Meijerman, Ignasio Manzanares, Jos H. Beijnen, Jan H M Schellens

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Thiocoraline is a potent new marine anti-cancer drug in vitro, which will be tested in phase I clinical studies shortly. To assess the biotransformation and the potential implications for human pharmacology and toxicology, the in vitro metabolism of thiocoraline was characterized using human plasma, human liver preparations, cytochrome P450 (CYP) and uridine diphosphoglucuronosyl transferase (UGT) supersomes and human cell lines. Thiocoraline is significantly metabolized by enzymes present in human plasma; t _1/2 shifted from 25.2 h in phosphate buffered saline to 4.3 h in human plasma. Using CYP supersomes it was shown that thiocoraline is mainly metabolized by CYP3A4, with CYP1A1, CYP2C8 and CYP2C9 playing a minor role in the biotransformation (

Original language	English
Pages (from-to)	241-251
Number of pages	11
Journal	Investigational New Drugs
Volume	22
Issue number	3
DOIs	https://doi.org/10.1023/B:DRUG.0000026250.34645.7f
Publication status	Published - Aug 2004

Keywords

Biotransformation
Conjugation
Cytochrome P450 (CYP)
Human cell lines
Human liver fractions
Supersomes
Thiocoraline
Uridine diphosphoglucuronosyl transferase (UGT)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1023/B:DRUG.0000026250.34645.7f

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title = "In vitro characterization of the biotransformation of thiocoraline, a novel marine anti-cancer drug",

abstract = "Thiocoraline is a potent new marine anti-cancer drug in vitro, which will be tested in phase I clinical studies shortly. To assess the biotransformation and the potential implications for human pharmacology and toxicology, the in vitro metabolism of thiocoraline was characterized using human plasma, human liver preparations, cytochrome P450 (CYP) and uridine diphosphoglucuronosyl transferase (UGT) supersomes and human cell lines. Thiocoraline is significantly metabolized by enzymes present in human plasma; t 1/2 shifted from 25.2 h in phosphate buffered saline to 4.3 h in human plasma. Using CYP supersomes it was shown that thiocoraline is mainly metabolized by CYP3A4, with CYP1A1, CYP2C8 and CYP2C9 playing a minor role in the biotransformation (",

keywords = "Biotransformation, Conjugation, Cytochrome P450 (CYP), Human cell lines, Human liver fractions, Supersomes, Thiocoraline, Uridine diphosphoglucuronosyl transferase (UGT)",

author = "Brandon, {Esther F A} and Rolf Sparidans and Irma Meijerman and Ignasio Manzanares and Beijnen, {Jos H.} and Schellens, {Jan H M}",

year = "2004",

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doi = "10.1023/B:DRUG.0000026250.34645.7f",

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AU - Brandon, Esther F A

AU - Sparidans, Rolf

AU - Meijerman, Irma

AU - Manzanares, Ignasio

AU - Beijnen, Jos H.

AU - Schellens, Jan H M

PY - 2004/8

Y1 - 2004/8

N2 - Thiocoraline is a potent new marine anti-cancer drug in vitro, which will be tested in phase I clinical studies shortly. To assess the biotransformation and the potential implications for human pharmacology and toxicology, the in vitro metabolism of thiocoraline was characterized using human plasma, human liver preparations, cytochrome P450 (CYP) and uridine diphosphoglucuronosyl transferase (UGT) supersomes and human cell lines. Thiocoraline is significantly metabolized by enzymes present in human plasma; t 1/2 shifted from 25.2 h in phosphate buffered saline to 4.3 h in human plasma. Using CYP supersomes it was shown that thiocoraline is mainly metabolized by CYP3A4, with CYP1A1, CYP2C8 and CYP2C9 playing a minor role in the biotransformation (

AB - Thiocoraline is a potent new marine anti-cancer drug in vitro, which will be tested in phase I clinical studies shortly. To assess the biotransformation and the potential implications for human pharmacology and toxicology, the in vitro metabolism of thiocoraline was characterized using human plasma, human liver preparations, cytochrome P450 (CYP) and uridine diphosphoglucuronosyl transferase (UGT) supersomes and human cell lines. Thiocoraline is significantly metabolized by enzymes present in human plasma; t 1/2 shifted from 25.2 h in phosphate buffered saline to 4.3 h in human plasma. Using CYP supersomes it was shown that thiocoraline is mainly metabolized by CYP3A4, with CYP1A1, CYP2C8 and CYP2C9 playing a minor role in the biotransformation (

KW - Biotransformation

KW - Conjugation

KW - Cytochrome P450 (CYP)

KW - Human cell lines

KW - Human liver fractions

KW - Supersomes

KW - Thiocoraline

KW - Uridine diphosphoglucuronosyl transferase (UGT)

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DO - 10.1023/B:DRUG.0000026250.34645.7f

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AN - SCOPUS:3543022079

SN - 0167-6997

VL - 22

SP - 241

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JO - Investigational New Drugs

JF - Investigational New Drugs

IS - 3

ER -

In vitro characterization of the biotransformation of thiocoraline, a novel marine anti-cancer drug

Abstract

Keywords

UN SDGs

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