Recent developments in predicting CYP-independent metabolism
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 |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:53 |
|---|---|
| Enthalten in: |
Drug metabolism reviews - 53(2021), 2 vom: 03. Mai, Seite 188-206 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Dhuria, Nikhilesh V [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 04.04.2022 Date Revised 05.04.2022 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1080/03602532.2021.1923728 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM324940564 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM324940564 | ||
| 003 | DE-627 | ||
| 005 | 20231225191402.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1080/03602532.2021.1923728 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1083.xml |
| 035 | |a (DE-627)NLM324940564 | ||
| 035 | |a (NLM)33941024 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Dhuria, Nikhilesh V |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Recent developments in predicting CYP-independent metabolism |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 04.04.2022 | ||
| 500 | |a Date Revised 05.04.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Non-CYP enzymes; alcohol and aldehyde dehydrogenase; aldehyde oxidase; carboxylesterase; flavin-containing monooxygenase; glutathione-S-transferase; monoamine oxidase; sulfotransferase; UDP glucuronosyltransferase; xanthine oxidase | |
| 650 | 7 | |a Cytochrome P-450 Enzyme System |2 NLM | |
| 650 | 7 | |a 9035-51-2 |2 NLM | |
| 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 | |
| 773 | 0 | 8 | |i Enthalten in |t Drug metabolism reviews |d 1973 |g 53(2021), 2 vom: 03. Mai, Seite 188-206 |w (DE-627)NLM000049530 |x 1097-9883 |7 nnns |
| 773 | 1 | 8 | |g volume:53 |g year:2021 |g number:2 |g day:03 |g month:05 |g pages:188-206 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1080/03602532.2021.1923728 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 53 |j 2021 |e 2 |b 03 |c 05 |h 188-206 | ||