Recent developments in predicting CYP-independent metabolism.
Drug Metab Rev
; 53(2): 188-206, 2021 05.
Article
in En
| MEDLINE
| ID: mdl-33941024
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Microsomes, Liver
/
Cytochrome P-450 Enzyme System
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Drug Metab Rev
Year:
2021
Document type:
Article
Affiliation country:
United States
Publication country:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM