부산대학교 도서관

This annual review is the sixth of its kind since 2016 (see references). Our objective is to explore and share articles which we deem influential and significant in the field of biotransformation and bioactivation. These fields are constantly evolving with new molecular structures and discoveries of corresponding pathways for metabolism that impact relevant drug development with respect to efficacy and safety. Based on the selected articles, we created three sections: (1) drug design, (2) metabolites and drug metabolizing enzymes, and (3) bioactivation and safety (Table 1). Unlike in years past, more biotransformation experts have joined and contributed to this effort while striving to maintain a balance of authors from academic and industry settings. Table 1. Articles covered in this review. Title First author Source Drug design 1 Metabolic and pharmaceutical aspects of fluorinated compounds BM Johnson J Med Chem 63: 6315–6386, 2020 2 Effective application of metabolite profiling in drug design and discovery MA Cerny J Med Chem 63: 6387–6406, 2020 3 Understanding the metabolism of proteolysis targeting chimeras (PROTACs): the next step toward pharmaceutical applications L Goracci J Med Chem 63: 11615–11638, 2020 4 Late-stage lead diversification coupled with quantitative nuclear magnetic resonance spectroscopy to identify new structure-activity relationship vectors at nanomole-scale synthesis: application to loratidine, a human histamine H1 receptor inverse agonist MS Lall J. Med. Chem 63: 7268–7292, 2020 5 GLORYx: prediction of the metabolites resulting from phase 1 and Phase 2 biotransformations of xenobiotics Christina de Bruyn Kops Chem Res Toxicol 34: 286–299, 2021 Metabolites & drug metabolizing enzymes 6 Inhibition of human UDP-glucuronosyltransferase (UGT) enzymes by kinase inhibitors: effects of dabrafenib, ibrutinib, nintedanib, trametinib and BIBF 1202. P. Korprasertthaworn Biochem Pharmacol 169: 113616, 2019 7 Highly selective inhibition of tyrosine kinase (TYK2) for the treatment of autoimmune diseases: discovery of the allosteric inhibitor BMS-986165 ST Wrobleski ST J Med Chem 62: 8973–8995, 2019 8 Discovery of a Novel deaminated metabolite of a single-stranded oligonucleotide in vivo by mass spectrometry Jing Li Bioanalysis 11: 1955–1966, 2019 9 In vitro metabolism of 2′‐ribose unmodified and modified phosphorothioate oligonucleotide therapeutics using liquid chromatography mass spectrometry Jaeah Kim Biomedical Chromatography 34: e4839, 2020 10 Excretion, mass balance, and metabolism of [14C]LY3202626 in humans: an interplay of microbial reduction, reabsorption, and aldehyde oxidase oxidation that leads to an extended excretion profile K Katyayan Drug Metab Dispos 48: 698–707, 2020 11 Novel homodimer metabolites of GDC-0994 via cytochrome P450-catalyed radical coupling RH Takahashi Drug Metab Dispos 48: 521–527, 2020 12 Metabolism and disposition of volanesorsen, a 2'- O-(2 methoxyethyl) antisense oligonucleotide, across species. N Post Drug Metab Dispos 47: 1164–1173, 2019 Bioactivation and safety 13 Novel o-toluidine metabolite in rat urine associated with urinary bladder carcinogenesis Y Tajima Chem Res Toxicol 33: 1907–1914, 2020 14 Identifying cysteine, N-Acetylcysteine, and glutathione conjugates as novel metabolites of aristolochic acid I: emergence of a new detoxifying pathway J Zhang Chem Res Toxicol. 33: 1374–1381, 2020 15 Significance of multiple bioactivation pathways for meclofenamate as revealed through modeling and reaction kinetics MA Schleiff Drug Metab Dispos 49: 133–141, 2021 16 Detoxication versus bioactivation pathways of lapatinib in vitro: UGT1A1 catalyzes the hepatic glucuronidation of debenzylated lapatinib. DT Nardone-White Drug Metab Dispos 49: 233–244, 2021 17 Discovery of JNJ-63576253: a clinical stage androgen receptor antagonist for F877L mutant and wild-type castration-resistant prostate cancer (mCRPC) Z Zhang J Med Chem 64: 909–924, 2021 18 Bioactivation of α,β-unsaturated carboxylic acids through acyl-glucuronidation T Mulder Drug Metab Dispos 48: 819–829, 2020 19 Strategies to mitigate the bioactivation of aryl amines C Zhang Chem Res Tox 33: 1950 − 1959, 2020 20 Investigation of clozapine and olanzapine reactive metabolite formation and protein binding by liquid chromatography-tandem mass spectrometry T Geib Chem Res Tox 33: 2420–2431, 2020 21 Application of a rat liver drug bioactivation transcriptional response assay early in drug development that informs chemically reactive metabolite formation and potential for drug-induced liver injury JJ Monroe Toxicol Sci 177: 281–299, 2020 [ABSTRACT FROM AUTHOR]