Drug-protein adducts

Evans, D.C. et al., Drug-protein adducts An industry perspective on minimizing the potential for drug bioactivation in drug discovery and development, Chem. Res. Toxicol., 17, 3, 2004. 

P450 3A and 2C forms in secondary metabolism and drug-protein adduct formation. Drug Metab Dispos 28(8) 945—950, 2000. 

The techniques described in this chapter can be of use to the optimization of lead compounds during drug discovery processes. However, the link between drug-protein adduct formation and toxicity has not been well defined. Additional considerations should be taken, such as therapeutic area and clinical doses. It has been suggested that a 10 mg daily dose rarely results in drug-related adverse effects (Uetrecht, 1999). Thus, the propensity of bioactivation should only be considered as one of the factors in the selection of developmental drug candidates. 

Zhou S. Separation and detection methods for covalent drug protein adducts. J Chromatogr B 2003 797 63-90. 

Localization of Drug-Protein Adducts in Animals Dosed with the Prototype Hepatotoxin, Acetaminophen... 

R 645 L. Zeng, C. H. Chen, M. Muller and M. -M. Zhou, Structure-Based Rational Design of Chemical Ligands for AMPA-Subtype Glutamate Receptors , J. Mol. Neurosci., 2003,20, 345 R 646 S. Zhou, Separation and Detection Methods for Covalent Drug-Protein Adducts , J. Chromatogr., B, 2003,797, 63 R 647 I. Zhukov and A. Ejchart, NMR Spectroscopy in Structural Proteomics. NMR-Based Protein Structure Determination , Polimery (Warsaw, Poland), 2003, 48, 28... 

Notley et al. (2002) investigated the P450 forms responsible for covalent drug-protein adduct formation and the possibility that covalent adduct formation might occur via alternative pathways to catechol formation. Recombinant P450 3A4 catalysed... 

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