Abstract
| Grant Number: | 5R44GM068164-03 |
| Project Title: | QSAR Models: Human CYP450 Drug Metabolism and Kinetics |
Abstract: DESCRIPTION (provided by applicant): The long-term objective of the proposed research is to provide computer-based tools to aid in the high-throughput screening of drug candidates, derived from combinatorial chemistry and similar techniques. The data for the QSAR models will be derived from human liver-based chromosome P450 enzymes. Three classes of models will be developed:
1. QSAR models for the estimation of Vmax and Km of various transformations. The Phase I application deals only with hydroxylation.
2. QSAR models for the estimation of probability of a compound being a substrate (or inhibitor) for a particular isozyme. The Phase I application deals only with CYP3A4.
3. QSAR models for intrinsic clearance, for various transformations. Again, the Phase I application deals only with hydroxylation.
The data for the kinetic models will be derived from the literature; the data for the substrate probability models from a previously assembled database of enzyme-compound relationships. Statistical techniques will include stepwise and all-possible regressions, the kNN-QSAR program based on a nearest-neighbor algorithm, as well as well as regression based on adaptive splines.
Thesaurus Terms:
chemical structure function, computer simulation, computer system design /evaluation, cytochrome P450, drug metabolism, high throughput technology, hydroxylation, molecular dynamics
chemical information system, chemical structure, combinatorial chemistry, enzyme substrate, isozyme, pharmacokinetics
Internet
| Institution: | ENSLEIN RESEARCH, INC. |
| SUITE 1428 |
| ROCHESTER, NY 14604 |
| Fiscal Year: | 2006 |
| Department: | |
| Project Start: | 01-APR-2004 |
| Project End: | 31-DEC-2007 |
| ICD: | NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES |
| IRG: | ZRG1 |
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