Valorization of a new technology for accelerating new drug development by improving early prediction of cardiac safety
Drug discovery and development is mainly based on trial and error, is inefficient, extremely time-consuming and risky for pharmaceutical companies, and too costly for society. Moreover, many drugs do not reach the market because of their side effects on the heart. Therefore, preclinical evaluation of adverse cardiac effects of drugs has become a priority for regulatory and pharmaceutical agencies.
This project aims to evaluate an innovative procedure to improve the cardiac safety assessment that all drugs must undergo before they are marketed. Our innovative technology allows characterisation of the kinetics of IKr or hERG blockade produced by a compound from data obtained with very simple experimental protocols, and automatically generates dynamic drug models using Markov model formulations. A key aspect of our technology is that it captures the nature (the electrophysiological characteristics) of the drug-IKr channel interactions, so the resulting models are able to faithfully reproduce these characteristics. Thus, the drug models generated with our technology are highly realistic, surpassing those obtained with the technique proposed by CiPA. In addition, the generation of the dynamic model of an IKr blocker from the data obtained with the experimental protocols is highly realistic, unlike those obtained with the technique proposed by CiPA.
This project will show that this technology predicts the effect of drugs much more accurately than the current technology, reaching a TRL7. This technology will accelerate the development of new drugs, thereby greatly reducing cost and time.
Project funded by Agència Valenciana de la Innovació and the European Union (INNVA1/2024/60).
Julio Gomis-Tena, Fernando Escobar, Lucia Romero. A simulation study of the impact of drug-IKr binding mechanisms on biomarkers of proarrhythmic risk reveals a crucial role in reverse use-dependence of action potential duration and a marked influence on the vulnerable window. Computer Methods and Programs in Biomedicine 260 (2025) 108566.
https://doi.org/10.1016/j.cmpb.2024.108566
