QSAR Models: Human CYP450 Drug Metabolism and Kinetics

Award Information
Agency:
Department of Health and Human Services
Branch:
N/A
Amount:
$411,379.00
Award Year:
2005
Program:
SBIR
Phase:
Phase II
Contract:
4R44GM068164-02
Agency Tracking Number:
GM068164
Solicitation Year:
2005
Solicitation Topic Code:
N/A
Solicitation Number:
PHS2005-2
Small Business Information
ENSLEIN RESEARCH, INC.
183 East Main Street, Suite 1428, Rochester, NY, 14604
Hubzone Owned:
N
Socially and Economically Disadvantaged:
N
Woman Owned:
N
Duns:
N/A
Principal Investigator
 KURT ENSLEIN
 (585) 232-8160
 KENSLEIN@ENRES.COM
Business Contact
 KURT ENSLEIN
Phone: (585) 232-8160
Email: KENSLEIN@ENRES.COM
Research Institution
N/A
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.

* information listed above is at the time of submission.

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