Reify Corporation
 machine visual screening for drug discovery and development
 
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Myosight™ Function
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Contraction Measurement
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IC50 Calculations

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Myosight™ Cardiac Function

Late stage failure of drugs due to cardiotoxicity is costly and has resulted in a number of drugs for a variety of indications being withdrawn from the market with combined potential losses in sales and sunk development costs in the billions of dollars. Cutting promising programs too early based on an incomplete understanding of their proarrhythmic potential is, clearly, another form of preventable loss. To appropriately evaluate early and late stage compounds for their proarrhythmic potential, Reify offers MyoSight™ as a high content alternative that captures the best aspects of patch clamping with the ability to measure fractional shortening in populations of cardiomyocytes. By providing data on all channels, either in isolation or in concert, Reify can provide you with a clearer picture to make better decisions earlier.

The current gold standard of patch clamp analysis of hERG can lead to useful information on potential TdP effects but because other ion channels are involved, screening using only this method potentially leads to dropping promising compounds. Examples of compounds currently on the market that are potent hERG channel blockers but do not lead to TdP include verapamil, amiodarone and others.

Engineered cells that include a variety of additional ion channels testable using patch clamping have been available for some time. These cells add relevant information but the process is hampered by throughput, cost and potential differences between model cells and native heart cells. To appropriately evaluate early and late stage compounds for their proarrhythmic potential, Reify offers MyoSight™ as a high content alternative that captures the best aspects of patch clamping with the ability to measure fractional shortening in populations of cardiomyocytes. By providing data on all channels, either in isolation or in concert, Reify can provide you with a clearer picture to make better decisions.

Outline of current techniques used in cardiotoxicity and their inherent limitations
Technique Attribute Challenge
Computational Screens
  • Potential to screen a large number of samples
  • Decreases number of hERG tests necessary
  • Training set-dependent results
  • Variations from set yield less accurate predictions
In vitro binding assays
  • Well established protocols and mathematical treatment
  • Can be compound specific
  • Cell and probe differences may lead to variable IC50 values
In vitro patch clamp assays
  • Sensitive ion flux measurement
  • Stable transfectants allow channel-specific read-out
  • Training set-dependent results
  • Variations from set yield less accurate predictions
In vivo assays
  • Canine model is gold standard for QT prolongation
  • Cost
  • Throughput
  • Not hightly correlative