Minimizing the risk of chemically reactive metabolite formation of new drug candidates: implications for preclinical drug design
Highlights•Reactive metabolite formation has been linked to drug-induced
toxicity.•Avoidance strategy widely applied in industry at early stages of drug discovery.•In …
toxicity.•Avoidance strategy widely applied in industry at early stages of drug discovery.•In …
Revisiting the metabolism and bioactivation of ketoconazole in human and mouse using liquid chromatography–mass spectrometry-based metabolomics
Although ketoconazole (KCZ) has been used worldwide for 30 years, its metabolic
characteristics are poorly described. Moreover, the hepatotoxicity of KCZ limits its …
characteristics are poorly described. Moreover, the hepatotoxicity of KCZ limits its …
Identification and characterization of in vitro phase I and reactive metabolites of masitinib using a LC-MS/MS method: bioactivation pathway elucidation
Masitinib is a selective tyrosine kinase inhibitor (TKI). It is currently registered in Europe for
the treatment of mast cell tumors in dogs. The current study reports the identification and …
the treatment of mast cell tumors in dogs. The current study reports the identification and …
Liabilities associated with the formation of “hard” electrophiles in reactive metabolite trapping screens
AS Kalgutkar - Chemical research in toxicology, 2017 - ACS Publications
Soft electrophiles (eg, epoxides, quinones, quinone-imines, quinone-methides, etc.)
generated via the oxidative bioactivation of phenyl, phenolic, amino-, and alkylphenolic …
generated via the oxidative bioactivation of phenyl, phenolic, amino-, and alkylphenolic …
In vitro ocular metabolism and bioactivation of ketoconazole in rat, rabbit and human
AL Cirello, JL Dumouchel, M Gunduz, CE Dunne… - Drug metabolism and …, 2017 - Elsevier
Oral ketoconazole is clinically administered for treatment of severe cases for fungal keratitis.
Pharmacodynamics and efficacy of oral and topical (ocular) ketoconazole have been …
Pharmacodynamics and efficacy of oral and topical (ocular) ketoconazole have been …
Monoamine oxidase B oxidizes a novel multikinase inhibitor KW-2449 to its iminium ion and aldehyde oxidase further converts it to the oxo-piperazine form in human
J Hosogi, R Ohashi, H Maeda, S Tashiro, E Fuse… - Drug Metabolism and …, 2017 - Elsevier
Abstract (E)-1-{4-[2-(1H-Indazol-3-yl) vinyl] benzoyl} piperazine (KW-2449) is a novel
multikinase inhibitor. During our clinical study, we found that KW-2449 is mainly metabolized …
multikinase inhibitor. During our clinical study, we found that KW-2449 is mainly metabolized …
Characterization of Nefazodone Time‐dependent Inhibition of Cytochrome P450 3A
Z Wang, BM Rock, JT Pearson, T Tran… - The FASEB …, 2017 - Wiley Online Library
Nefazodone (Serzone®), marketed as an antidepressant, was discontinued in 2004 due to
the rare incidence of hepatoxicity. In vitro studies focused on characterizing the metabolism …
the rare incidence of hepatoxicity. In vitro studies focused on characterizing the metabolism …
Non-Dissociative Sequential Metabolism of Enoxacin to a Metabolic Intermediate Complex with Cytochrome P450 1A2
RP Seguin - 2017 - digital.lib.washington.edu
Cytochrome P450 enzymes constitute a superfamily of isoforms which accelerate the
removal of foreign compounds from the body through oxidative biotransformation to …
removal of foreign compounds from the body through oxidative biotransformation to …
[引用][C] Stable isotope labelling and computational data mining approaches in drug metabolism studies
MG Leeming - 2017