Computational Tools and Resources for Metabolism-related Property Predictions. 2. Application to Prediction of Half-life Time in Human Liver Microsomes

Overview

Journal Future Med Chem

Specialties Chemistry
Pharmacy

Date 2012 Oct 24

PMID 23088274

Citations 11

Authors

Alexey V Zakharov

Megan L Peach

Markus Sitzmann

Igor V Filippov

Heather J McCartney

Layton H Smith

Angelo Pugliese

Marc C Nicklaus

Affiliations

Soon will be listed here.

Abstract

Background: The most important factor affecting metabolic excretion of compounds from the body is their half-life time. This provides an indication of compound stability of, for example, drug molecules. We report on our efforts to develop QSAR models for metabolic stability of compounds, based on in vitro half-life assay data measured in human liver microsomes.

Method: A variety of QSAR models generated using different statistical methods and descriptor sets implemented in both open-source and commercial programs (KNIME, GUSAR and StarDrop) were analyzed. The models obtained were compared using four different external validation sets from public and commercial data sources, including two smaller sets of in vivo half-life data in humans.

Conclusion: In many cases, the accuracy of prediction achieved on one external test set did not correspond to the results achieved with another test set. The most predictive models were used for predicting the metabolic stability of compounds from the open NCI database, the results of which are publicly available on the NCI/CADD Group web server ( http://cactus.nci.nih.gov ).

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