COMPACT: A structural approach to the modelling of cytochromes P450 and their interactions with xenobiotics

Journal of Chemical Technology and Biotechnology

Volumn 76, Issue 3, 2001, Pages 237-244

  Lewis, David F V ^a  

^a UNIVERSITY OF SURREY   (United Kingdom)

Author keywords

COMPACT (computer optimized molecular parametric analysis of chemical toxicity; Cytochromes P450; QSAR (quantitative structure activity relationship)

Indexed keywords

CARCINOGEN; CYTOCHROME P450; CYTOCHROME P450 ISOENZYME; XENOBIOTIC AGENT;

CARCINOGENICITY; CHEMICAL ANALYSIS; CHEMICAL STRUCTURE; COMPUTER ANALYSIS; COMPUTER SYSTEM; DRUG METABOLISM; DRUG SAFETY; ENZYME ACTIVITY; ENZYME INDUCTION; ENZYME SPECIFICITY; ENZYME SUBSTRATE COMPLEX; EVALUATION; METABOLIC ACTIVATION; MOLECULAR INTERACTION; NONHUMAN; QUANTITATIVE STRUCTURE ACTIVITY RELATION; REVIEW; RISK ASSESSMENT; SEQUENCE HOMOLOGY; TOXICITY TESTING;

MAMMALIA;

EID: 0035114457     PISSN: 02682575     EISSN: None     Source Type: Journal    
DOI: 10.1002/jctb.363     Document Type: Review

References (53)

1. P450 superfamily: Update on new sequences, gene mapping, accession numbers and nomenclature
2. Sex and drugs and P450
3. Molecular dimensions of the substrate binding site of cytochrome P-448
4. Molecular orbital studies of oxygen activation and mechanisms of cytochromes P450-mediated oxidative metabolism of xenobiotics
5. Prediction of chemical carcinogenicity from molecular and electronic structures: A comparison of MINDO/3 and CNDO/2 molecular orbital methods
6. Molecular modelling of CYP2E1 enzymes from rat, mouse and man: An explanation for species differences in butadiene metabolism and potential carcinogenicity, and rationalization of CYP2E substrate specificity
7. Validation of a novel molecular orbital approach (COMPACT) for the prospective safety evaluation of chemicals by comparison with rodent carcinogenicity and salmonella mutagenicity data evaluated by the U.S. NCI/NTP
8. Further validation of COMPACT, the molecular orbital approach for the prospective safety evaluation of chemicals: Incorporation of log P values. Re-evaluation of 200 miscellaneous chemicals by comparison with rodent carcinogenicity and salmonella mutagenicity data from the U.S. NCI/NTP
9. Molecular modelling of enzymes and receptors involved in carcinogenesis
10. Computer-assisted methods in the evaluation of chemical toxicity
11. Computer modelling of cytochromes P-450 and their substrates: A rational approach to the prediction of carcinogenicity
12. Comparison between rodent carcinogenicity test results of 44 chemicals and a number of predictive systems
13. A comparison between COMPACT and HazardExpert evaluations for 80 chemicals tested by the NTP/NCI rodent bioassay
14. A retrospective evaluation of COMPACT predictions of the outcome of NTP rodent carcinogenicity testing
15. A validation study of the COMPACT and HazardExpert techniques with 40 chemicals
16. Risk assessment: Molecular modelling
17. The development and validation of expert systems for predicting toxicity
18. Molecular modelling of members of the P4502A subfamily: Application to studies of enzyme specificity
19. Molecular modelling of CYP1A subfamily members: Rationalization of CYP1A substrate specificity in terms of active site amino acid residues
20. Molecular modelling of mammalian CYP2B isoforms and their interaction with substrates, inhibitors and redox partners
21. Molecular modelling of mammalian cytochromes P450 and evaluation of chemical toxicity and metabolism using COMPACT
22. Molecular modelling of CYP3A4 from an alignment with CYP102: Identification of key interactions between putative active site residues and CYP3A-specific chemicals
23. Molecular modelling of cytochrome P4502D6 (CYP2D6) based on an alignment with CYP2D6: Structural studies on specific CYP2D6 substrate metabolism
24. Molecular modelling of human CYP2C subfamily enzymes CYP2C9 and CYP2C19: Rationalization of substrate specificity and site-directed mutagenesis experiments in the CYP2C subfamily
25. bm3)
26. Nitrosamine carcinogenesis: Quantitative structure-activity relationships and human risk assessment
27. Molecular orbital calculations and quantitative structure-activity relationships for some polyaromatic hydrocarbons
28. The genotoxicity of benzanthracenes: A quantitative structure-activity study
29. Structure-activity models for toxicity testing
30. Molecular orbital-generated QSARs in a homologous series of alkoxyresorufins and studies of their interactive docking with P450s
31. Computer graphics analysis of the interaction of alkoxy methylenedioxybenzenes with cytochromes P4501
32. Quantitative structure-activity relationships in some cooked food mutagens
33. Inhibition of rat hepatic aryl hydrocarbon hydroxylase activity by a series of 7-hydroxy coumarins: QSAR studies
34. The interaction of a homologous series of hydrocarbons with hepatic cytochrome P450: Molecular orbital-derived electronic and structural parameters influencing the haemoprotein spin state
35. A quantitative structure-activity relationship study on a series of 10 para-substituted toluenes binding to cytochrome P4502B4 (CYP2B4), and their hydroxylation rates
36. Quantitative structure-activity relationships in a series of alcohols exhibiting inhibition of cytochrome P450-mediated aniline hydroxylation
37. Interaction of a series of nitriles with the alcohol-inducible isoform of P450: Computer analysis of structure-activity relationships
38. Quantitative structure-activity relationships in a series of endogenous and synthetic steroids exhibiting induction of CYP3A activity and hepatomegaly associated with increased DNA synthesis
39. The interaction of some peroxisome proliferators with the mouse liver peroxisome proliferator-activated receptor (ppar): A molecular modelling and quantitative structure-activity study
40. Quantitative structure-activity relationship (QSAR) analysis for a series of rodent peroxisome proliferators: Interaction with the mouse liver peroxisome proliferator-activated receptor α (mPPARα)
41. The CYP4 family
42. Molecular modelling of omeprazole interactions with cytochrome P450 isozymes is consistent with metabolism in human liver microsomes
43. The metabolism of tamoxifen by human cytochromes P450 is rationalized by molecular modelling of the enzyme-substrate interactions: Potential importance to its proposed anti-carcinogenic/carcinogenic actions
44. In vitro metabolism of side-chain cleaved dexamethasone (9αF-A) is CYP3A4 mediated; rationalization of CYP3A4 and CYP17 (17, 20 lyase) involvement in dexamethasone metabolism in vitro based on molecular modelling studies
45. Structure-activity relationships in the metabolism of a series of tertiary amines by cytochrome P450
46. Induction of cytochrome P4501 as an indicator of potential carcinogenesis
47. Quantitative structure-activity relationships in substrates, inducers and inhibitors of cytochrome P4501 (CYP1)
48. Molecular modelling of cytochromes P450
49. COMPACT and the importance of frontier orbitals in toxicity mediated by the cytochrome P450 mono-oxygenase system
50. Frontier orbitals in chemical and biological activity: Quantitative relationships and mechanistic implications