Quantitative structure activity relationships in drug metabolism.
This review of 61 references delineates contemporary computation quantitative structure activity relationship (QSAR) approaches that have been used to elucidate the molecular features that influence the binding and metabolism of a compound by the major phase 1 and phase 2 metabolising enzymes; Cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT), respectively. Contemporary studies are applying 2D and 3D QSAR, pharmacophore approaches and nonlinear techniques (for example: recursive partitioning, neural networks and support vector machines) to model drug metabolism. Furthermore, this review highlights some of the challenges and opportunities for future research; the need to develop 'global' models for CYP and UGT metabolism and to extend QSAR for other important metabolising enzymes.
Chohan
Kamaldeep K
KK
Department of Physical & Metabolic Sciences, AstraZeneca R&D Charnwood, Bakewell Road, Loughborough, Leicestershire LE11 5RH, UK. Kamaldeep.Chohan@ astrazeneca.com
Paine
Stuart W
SW
Waters
Nigel J
NJ
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D014453:Glucuronosyltransferase / Q000378:metabolism*; D006801:Humans; D008658:Inactivation, Metabolic; D021281:Quantitative Structure-Activity Relationship
D003577:Cytochrome P-450 Enzyme System; D014453:Glucuronosyltransferase