Recent developments in predicting CYP-independent metabolism / Nikhilesh V. Dhuria, Bianka Haro, Amit Kapadia, Khadjia A. Lobo, Bernice Matusow, Mary A. Schleiff, Christina Tantoy, Jasleen K. Sodhi
Abstract As lead optimization efforts have successfully reduced metabolic liabilities due to cytochrome P450 (CYP)-mediated metabolism, there has been an increase in the frequency of involvement of non-CYP enzymes in the metabolism of investigational compounds. Although there have been numerous notable advancements in the characterization of non-CYP enzymes with respect to their localization, reaction mechanisms, species differences and identification of typical substrates, accurate prediction of non-CYP-mediated clearance, with a particular emphasis with the difficulties in accounting for any extrahepatic contributions, remains a challenge. The current manuscript comprehensively summarizes the recent advancements in the prediction of drug metabolism and the in vitro to in vitro extrapolation of clearance for substrates of non-CYP drug metabolizing enzymes.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:53 |
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| Enthalten in: |
Drug metabolism reviews - 53(2021), 2, Seite 188-206 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Dhuria, Nikhilesh V. [VerfasserIn] |
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| Links: |
FID Access [lizenzpflichtig] |
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| Themen: |
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| Umfang: |
1 Online-Ressource (19 p) |
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| doi: |
10.1080/03602532.2021.1923728 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Abstract As lead optimization efforts have successfully reduced metabolic liabilities due to cytochrome P450 (CYP)-mediated metabolism, there has been an increase in the frequency of involvement of non-CYP enzymes in the metabolism of investigational compounds. Although there have been numerous notable advancements in the characterization of non-CYP enzymes with respect to their localization, reaction mechanisms, species differences and identification of typical substrates, accurate prediction of non-CYP-mediated clearance, with a particular emphasis with the difficulties in accounting for any extrahepatic contributions, remains a challenge. The current manuscript comprehensively summarizes the recent advancements in the prediction of drug metabolism and the in vitro to in vitro extrapolation of clearance for substrates of non-CYP drug metabolizing enzymes | ||
| 653 | |a Non-CYP enzymes; alcohol and aldehyde dehydrogenase; aldehyde oxidase; carboxylesterase; flavin-containing monooxygenase; glutathione-S-transferase; monoamine oxidase; sulfotransferase; UDP glucuronosyltransferase; xanthine oxidase | ||
| 700 | 1 | |a Haro, Bianka |e verfasserin |4 aut | |
| 700 | 1 | |a Kapadia, Amit |e verfasserin |4 aut | |
| 700 | 1 | |a Lobo, Khadjia A. |e verfasserin |4 aut | |
| 700 | 1 | |a Matusow, Bernice |e verfasserin |4 aut | |
| 700 | 1 | |a Schleiff, Mary A. |e verfasserin |4 aut | |
| 700 | 1 | |a Tantoy, Christina |e verfasserin |4 aut | |
| 700 | 1 | |a Sodhi, Jasleen K. |e verfasserin |4 aut | |
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