Is your most potent compounds also safe?

The Safe Lead Select line of services is particularly targeted to the candidate selection process which precedes the bona fide drug development process.  The assays included therein are designed to be predictive, robust, and economical.  In selecting the number of tissues, concentrations, and parameters evaluated, particular consideration has been given to maintaining a high statistical power, therefore maximizing the reliability of the results generated.

In addition, the assays are also meant to provide a rapid quantitative assessment of the cardiac liability associated with each of a large number of compounds. In essence, the Safe Lead Select assays represent scaled down versions of the full-size, functional assays being performed prior to IND submission, for a fraction of the price.

Safe Lead Select assays are:

• Automated hERG^SCREEN
  Functional hERG/Kv11.1 Potassium Channel inhibition assay using the Patch Express 7000 automated patch clamp system
  Protocol outline:
  
  • TA tested in 3 cells at 3 concentrations on HEK 293 cell stably transfected with the hERG gene.
  • Cisapride as positive control, IC50 determination
    Click here for more
    
    
    
• Manual hERG^SCREEN
  Rapid delayed rectifying potassium (IKr) current inhibition assay using manual whole-cell patch clamp technique
  Protocol outline:
  
  • TA tested in 3 cells at 3 concentrations on CHO or HEK 293 cells stably transfected with the hERG gene.
  • Cisapride, dofetilide or E-4031 as positive control
    Click here for more
    
    
    
• APD^SCREEN
  Action Potential Duration analysis in purkinje fibres or contractile cardiac tissue.
  Protocol outline:
  
  • TA tested in 3 tissues at 3 concentrations
    
  • E-4031 as positive control
    
  • Amplitude of the action potential, rate of depolarisation, APD30, 60, 90 determined
    Click here for more
    
    
    
• In-Vivo/In-Vitro QT^SCREEN
  Study package including manual hERG^screen & in-vivo ECG in small animal
  Protocol outline:
  
  • hERG: TA tested in 3 cells at 3 concentrations on HEK 293 cell stably transfected with the hERG gene.
    
  • In-vivo ECG and arterial blood pressure in conscious and surgically instrumented
    animals, with suitable DSI telemetry monitoring
  • Cisapride, dofetilide or E-4031 as positive control
    Click here for more
    
    
    
• E-C coupling^SCREEN
  Simultaneous APD and contraction measurements
  Protocol outline:
  
  • TA tested in 3 tissues at 3 concentrations
    
  • Cisapride, dofetilide or E-4031 as positive control
    Click here for more