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Rapid in silico selection of an MCHR1 antagonists’ focused library from multi-million compounds’ repositories: biological evaluation

Abstract

Target-focused libraries can be rapidly selected by 2D virtual screening methods from multimillion compounds’ databases if structures of active compounds are available. In the present study, a multi-step virtual and in vitro screening cascade is used to select melanin-concentrating hormone receptor-1 antagonists. The 2D similarity search combined with physico-chemical parameter filtering is suitable for selecting candidates from multimillion compounds’ repository. The seeds of the first round of virtual screening were collected from literature commercial databases, whereas the seeds of the second round were the hits the first round of biological testing In vitro screening underlined the efficiency of our approach, as in the second screening round the hit rate (8.6 %) significantly improved compared to the first round (1.9 %), applying a strict requirement for hit selection, and also this cascade-like screening method was appropriate for selecting several compounds reaching efficacies even below 10 nM.

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Notes

  1. 1.

    www.chembridge.com, www.chemdiv.com, www.asinex.com, www.enamine.net, www.lifechemicals.com, www.ukrorgsynth.com, www.amriglobal.com, www.specs.net, www.maybridge.com, www.ibscreen.com.

  2. 2.

    http://www.chemaxon.com (accessed April, 2010); InstJChem v. 5.3.1, 2010 was used for structure searching and chemical database access and management: Marvin v. 5.3.1, 2010 was used for drawing, displaying, and characterizing chemical structures and substructures: fingerprints are explained at: http://www.chemaxon.com/jchem/doc/user/fingerprint.html.

Abbreviations

MCHR1:

Melanine concentrating hormone receptor-1

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Acknowledgments

This work was partially supported by the National Development Agency (NFÜ) Grant: #KMOP-1.1.1-09/1-2009-0051).

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Correspondence to György Dormán.

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Flachner, B., Tömöri, T., Hajdú, I. et al. Rapid in silico selection of an MCHR1 antagonists’ focused library from multi-million compounds’ repositories: biological evaluation. Med Chem Res 23, 1234–1247 (2014). https://doi.org/10.1007/s00044-013-0695-0

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Keywords

  • 2D similarity selection
  • Virtual screening
  • MCHR1 antagonists
  • In vitro screening