Pharmacophore-based discovery of new human dihydroorotate dehydrogenase inhibitor

Peng Lu, Yubin Wang, Bo Ma, Jinxiong She, Qi Zhang, Mingfang He, Ying Liu

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)402-408
Number of pages7
JournalMedicinal Chemistry
Volume10
Issue number4
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

Fingerprint

Inhibitory Concentration 50
Chemical Databases
Random Allocation
Hydrogen
Costs and Cost Analysis
dihydroorotate dehydrogenase

Keywords

  • Discovery studio
  • Drug discovery
  • Human DHODH inhibitor
  • HypoGen
  • Pharmacophore
  • Virtual screening

ASJC Scopus subject areas

  • Drug Discovery

Cite this

Pharmacophore-based discovery of new human dihydroorotate dehydrogenase inhibitor. / Lu, Peng; Wang, Yubin; Ma, Bo; She, Jinxiong; Zhang, Qi; He, Mingfang; Liu, Ying.

In: Medicinal Chemistry, Vol. 10, No. 4, 01.01.2014, p. 402-408.

Research output: Contribution to journalArticle

Lu, Peng ; Wang, Yubin ; Ma, Bo ; She, Jinxiong ; Zhang, Qi ; He, Mingfang ; Liu, Ying. / Pharmacophore-based discovery of new human dihydroorotate dehydrogenase inhibitor. In: Medicinal Chemistry. 2014 ; Vol. 10, No. 4. pp. 402-408.
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