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Internet Electronic Journal of Molecular Design - IEJMD, ISSN 1538-6414, CODEN IEJMAT
| ABSTRACT - Internet Electron. J. Mol. Des. September 2004, Volume 3, Number 9, 586-609 |
3D-QSAR of Protein Tyrosine Phosphatase 1B Inhibitors by Genetic
Function Approximation
Sree M. Vadlamudi and Vithal M. Kulkarni
Internet Electron. J. Mol. Des. 2004, 3, 586-609
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Abstract:
Protein tyrosine phosphatase 1B (PTP 1B) has been implicated as
negative regulator of insulin receptor signaling system. Design of
small molecule PTP 1B inhibitors has received considerable
attention as inhibition of PTP 1B enzyme is expected to improve
insulin action, to treat non-insulin dependent diabetes mellitus
(NIDDM). In this work, we report three dimensional quantitative
structure activity relationship (3D-QSAR) study performed by
genetic function approximation (GFA) technique on a series of
benzofuran/benzothiophene biphenyls as PTP 1B inhibitors. The
QSAR models were generated using 92 compounds, and the
predictive ability of the resulting each model was evaluated against
a test set of 26 compounds. The internal (correlation coefficient r2)
and external consistency (predictive r2) of the final QSAR model
was 0.694 and 0.672 respectively. Analyses of results from the
present QSAR study indicate that electronic, structural, and shape
descriptors govern the PTP 1B inhibitory activity.
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