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Positioning

Where Equinox Pharma has positioned itself

INDDEx™

Technology and methodology behind INDDEx™

Advantages

Advantages of using INDDEx™ over other technologies

Targets

Results of INDDEx™ application to various targets

Publications

Publications relating to Equinox Pharma technologies

Hit discovery on targets

Targets index

 

Cannabinoid receptor 1

Strapline needed

  • INDDEx™ was used in a blind in-house trial
  • Aim was to find novel antagonists against the GPCR cannabinoid receptor 1 (CB1)
  • Obtained training data on activity from publicly-available literature
  • Screened ZINC database with 5 million available compounds
  • Experimentally tested 157 molecules
  • 2 hits had IC50 < 1μM
  • 26 hits had 1μM < IC50 < 12μM
  • Most hits were chemically diverse from training data
  • Results available from Equinox Pharma

Flowchart of the blind trial process applied to the screening of target CB1. Observed activity => INDDEx => 250 in silico hits from database of 5M => 157 compounds ordered => 28 verified in vitro hits

Distribution of hits by activity: Histogram depicting distribution of diversity for the CB1 receptor screening, showing the number of hits at varying levels of Tanimoto similarity to any of the molecules in the training data

Distribution of hits based on their diversity (Tanimoto coefficients):

Dopamine D1 receptor

Strapline needed

  • INDDEx™ used in a blind in-house trial
  • Aim was to find novel antagonists against the GPCR dopamine receptor 1 (DR1)
  • Obtained high quality training data on activity from Cerep
  • Screened ZINC database with 5 million available compounds
  • Experimentally tested 94 molecules
  • 2 hits had IC50 < 0.1μM
  • 8 hits had 0.1μM < IC50< 1μM
  • 16 hits had 1μM < IC50 < 10μM
  • Most hits were chemically diverse from training data
  • Results available from Equinox

Flowchart of the blind trial process applied to the screening of target DR1. Observed activity => INDDEx => 250 in silico hits from database of 5M => 94 compounds ordered => 30 verified in vitro hits

Distribution of hits by activity: Histogram depicting distribution of hit activity for the Dopamine D1 receptor screening, showing the number of hits at varying levels of IC50 activity

Distribution of hits based on their diversity (Tanimoto coefficients): Histogram depicting distribution of diversity for the Dopamine D1 receptor screening, showing the number of hits at varying levels of Tanimoto similarity to any of the molecules in the training data

 

NAD-dependent deacetylase sirtuin-2 (SIRT2)

Strapline needed

Model learned from only seven active molecules found

  • INDDEx™ used for a medicinal chemistry research project in academia
  • Aim was to find novel antagonists against the SIRT2 protein that were structurally distinct and selective for SIRT2 over other sirtuin proteins
  • Training data taken from known structure-activity results published in literature
  • Training data included only seven active molecules with activities from 1.5μM to 78μM, as well as 13 inactives
  • Screened ZINC 12 database with 25 million available compounds
  • The top 200 molecules ranked by INDDEx™ were tested against the SIRT2 crystal structure using GOLD docking software
  • The top 50 molecules ranked by GOLD were clustered by structure
  • Experimentally tested 8 molecules
  • One hit with IC50 of 0.7μM (better than any previously known) and another with IC50 of 3.9┬ÁM
  • Both molecules structurally distinct from previously known actives
  • Results to be published