LeadBuilder - Virtual Hit Screening

computational modelling

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To identify small molecule starting points for a drug discovery program, Domainex has successfully used its LeadBuilder virtual screening platform across a large number of programmes, against targets as diverse as kinases, proteases, protein-protein interactions, methyltransferases and ion channels. Many of these programmes are now at the Candidate Drug stage, with a selection currently in the clinic.

Domainex's LeadBuilder hit identification technology delivers and is highly efficient. Domainex’s approach to the virtual screening of these compounds is what differentiates it from others, as screening libraries are pre-curated to be 'developable'.  This means that when hits are identified by Domainex, you can be confident that phys chem properties will not be a barrier to progressing your drug discovery programme!

Key advantages of LeadBuilder are:

  • No need to screen 100,000s compounds.  Typically only 1000 compounds screened to identify hits
  • Hits are pre-curated to ensure 'developability' and streamlined hit-to-lead chemistry
  • Fast!  Only 3-4 months to identify hits for validation
  • High success rate of >93% across target classes
  • Homology models or ligand-based pharmacophores can be built to enable screening set to be identified when target structural information is absent


High Hit Rate and Success Across Target Classes

LeadBuilder has been successfully used by Domainex to identify focussed screening sets which have a high hit-rate in biological assays.  With a success rate of >93% across targets as diverse as kinases, protein-protein interactions, proteases and lysine methyltransferases, LeadBuilder delivers! 

A typical random screen of 100,000s compounds might have a hit-rate in a biochemical assay of 0.01-0.1%, whereas we often find that LeadBuilder affords screening sets of only 1000 compounds with hit-rates of between 1-10%. In the two cases where our clients made side-by-side comparisons of LeadBuilder with other vendors’ proprietary focussed libraries, LeadBuilder set gave 10-fold higher hit-rates. Furthermore, the excellent property profile of LeadBuilder hits means that they are suitable for rapid progression towards candidate drugs, and we have several examples where this has been achieved within two years.

This approach is highly efficient (only 3-4 months to deliver hits), and when LeadBuilder is coupled to Domainex's Combinatorial Domain Hunting (CDH) platform, early discovery timelines can be significantly reduced.  CDH-LeadBuilder when combined, cut typical timelines of 18 months down to only 8-9 months from target protein expression and assay development to hit series (Pammolli et al., 2011). In addition, the resultant hits from LeadBuilder are derived from Domainex’s pre-filtered compound screening database, so are developable and already exhibit lead-like properties, resulting in reduced hit-to-lead phase timelines (typically only 6 months for Domainex hits).


Fabio Pammolli, Laura Magazzini & Massimo Riccaboni (2011). The productivity crisis in pharmaceutical R&D. Nature Reviews Drug Discovery, 10, 428-438