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Weidlich IE, Dexheimer TS, Marchand C, et al. Virtual screening using ligand-based pharmacophores for inhibitors of human tyrosyl-DNA phospodiesterase (hTdp1). Bioorg Med Chem. 2010;18(6):2347-2355doi: 10.1016/j.bmc.2010.02.009.
Weidlich, I. E., Dexheimer, T. S., Marchand, C., Antony, S., Pommier, Y., & Nicklaus, M. C. (2010). Virtual screening using ligand-based pharmacophores for inhibitors of human tyrosyl-DNA phospodiesterase (hTdp1). Bioorganic & medicinal chemistry, 18(6), 2347-2355. https://doi.org/10.1016/j.bmc.2010.02.009
Weidlich, Iwona E, et al. "Virtual screening using ligand-based pharmacophores for inhibitors of human tyrosyl-DNA phospodiesterase (hTdp1)." Bioorganic & medicinal chemistry vol. 18,6 (2010): 2347-2355. doi: https://doi.org/10.1016/j.bmc.2010.02.009
Weidlich IE, Dexheimer TS, Marchand C, Antony S, Pommier Y, Nicklaus MC. Virtual screening using ligand-based pharmacophores for inhibitors of human tyrosyl-DNA phospodiesterase (hTdp1). Bioorg Med Chem. 2010 Mar 15;18(6):2347-2355. doi: 10.1016/j.bmc.2010.02.009. Epub 2010 Mar 02. PMID: 30025429.
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Bioorg Med Chem. 2010 Mar 15;18(6):2347-2355. doi: 10.1016/j.bmc.2010.02.009. Epub 2010 Mar 02.

Virtual screening using ligand-based pharmacophores for inhibitors of human tyrosyl-DNA phospodiesterase (hTdp1).

Bioorganic & medicinal chemistry

Iwona E Weidlich, Thomas S Dexheimer, Christophe Marchand, Smitha Antony, Yves Pommier, Marc C Nicklaus

Affiliations

  1. Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, DHHS, Frederick, MD 21702, USA.
  2. Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, DHHS, Bethesda, MD 20892, USA.

PMID: 30025429 DOI: 10.1016/j.bmc.2010.02.009

Abstract

Human tyrosyl-DNA phosphodiesterase (hTdp1) inhibitors have become a major area of drug research and structure-based design since they have been shown to work synergistically with camptothecin (CPT) and selectively in cancer cells. The pharmacophore features of 14hTdp1 inhibitors were used as a filter to screen the ChemNavigator iResearch Library of about 27 million purchasable samples. Docking of the inhibitors and hits obtained from virtual screening was performed into a structural model of hTdp1 based on a high resolution X-ray crystal structure of human Tdp1 in complex with vanadate, DNA and a human topoisomerase I (Top1)-derived peptide (PDB code: 1NOP). We present and discuss in some detail 46 compounds matching the three-dimensional arrangement of the pharmacophoric features. The presented novel chemotypes may provide new scaffolds for developing inhibitors of Tdp1.

Copyright © 2010. Published by Elsevier Ltd.

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