Abstract
Pharmacophore models of human dihydroorotate dehydrogenase (HsDHODH) have been developed using Discovery Studio V2.1 with a training set of 27 HsDHODH inhibitors. With one hydrogen bond receptor, two hydrophobic, one ring aromatic and one neg ionizable features, Hypo 1 has a correlation coefficient of 0.948, cost difference of 78.894, and RMSD 0.926. This model was validated by test set and Fischer randomization test. Hypo 1 was employed as a 3D query to identify potent molecules from our lab chemical database. Compound 38-C11 had Hypo 1 estimated IC50 of 489 nM. Then 38-C11 was synthesized and evaluated in HsDHODH inhibition assay. The IC50 of 38-C11 was 136.9 nM suggesting that 38-C11 could be proceeded for further evaluation in future study.
Keywords: Human DHODH inhibitor, discovery studio, drug discovery, hypoGen, pharmacophore, virtual screening.
Medicinal Chemistry
Title:Pharmacophore-Based Discovery of New Human Dihydroorotate Dehydrogenase Inhibitor
Volume: 10 Issue: 4
Author(s): Peng Lu, Yubin Wang, Bo Ma, Jinxiong She, Qi Zhang, Mingfang He and Ying Liu
Affiliation:
Keywords: Human DHODH inhibitor, discovery studio, drug discovery, hypoGen, pharmacophore, virtual screening.
Abstract: Pharmacophore models of human dihydroorotate dehydrogenase (HsDHODH) have been developed using Discovery Studio V2.1 with a training set of 27 HsDHODH inhibitors. With one hydrogen bond receptor, two hydrophobic, one ring aromatic and one neg ionizable features, Hypo 1 has a correlation coefficient of 0.948, cost difference of 78.894, and RMSD 0.926. This model was validated by test set and Fischer randomization test. Hypo 1 was employed as a 3D query to identify potent molecules from our lab chemical database. Compound 38-C11 had Hypo 1 estimated IC50 of 489 nM. Then 38-C11 was synthesized and evaluated in HsDHODH inhibition assay. The IC50 of 38-C11 was 136.9 nM suggesting that 38-C11 could be proceeded for further evaluation in future study.
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Cite this article as:
Lu Peng, Wang Yubin, Ma Bo, She Jinxiong, Zhang Qi, He Mingfang and Liu Ying, Pharmacophore-Based Discovery of New Human Dihydroorotate Dehydrogenase Inhibitor, Medicinal Chemistry 2014; 10 (4) . https://dx.doi.org/10.2174/15734064113096660047
DOI https://dx.doi.org/10.2174/15734064113096660047 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
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