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Poster: Novel 3D Primary Human Cardiomyocyte Culture System for Evaluation of Candidate Drug Related Cardiac Safety Profile

Introduction

Drug discovery and development are hampered by high attrition rates that are

largely attributed to the reliance on model systems that are minimally

representative of the underlying human biology. Although the animal models

are a good overall proof of concept, safety and efficacy evaluations in such

models are hard to extrapolate to the human situation. Thus, there is an

urgent need for high-throughput human in-vitro cell based assay systems to

predict safety profile of drugs for cardiac related ailments prior to clinical

evaluation. Such human in vitro culture systems can be utilized in

mechanism-based assays for cardiotoxicity assessment. It is becoming

increasingly apparent that human primary cardiomyocytes can serve as the

biological and physiological relevant in-vitro model system for drug discovery/

cardiotoxicity screens. In this study we screened 10 potential newly

synthesized small molecules: CEP2001,2002,2003,2004, 2005, 2006,

2007,2008, 2009 and 2010. These molecules were screened for their toxicity

and electro-physiological activities in a 3D cardiac cell based assay. Of the 10

molecules that were screened, we found CEP2005 & CEP2010 to enhance the

electro-physiological activity when compared to the untreated controls. The

IC₅₀ values for CEP2005 are 5ng /ml and CEP2010 25 ng /ml determined from

3D cardiac model system. 

 

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