Avoiding Structural Activity Relationships (SAR) littered with cardiovascular risk
Clyde has developed a primary screening assay with a large pharma to help identify compounds with a CV liability at the hit-to-lead/lead optimisation phases
The aim is to avoid troublesome SAR so that cardiovascular liability can be designed out via computational and medicinal chemistry at an early stage, avoiding costly failures later in development
Typically larger batches of compounds are screened for
Effects on spontaneously beating hiPSC cardiomyocytes
hERG, Cav and Nav effects
Proarrhythmic risk
Effects on excitability
APD90 prolongation
Triangulation
EADs
Primary Screening – Typical Data
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