Abstract
Toxicity related failures in drug discovery and clinical development have motivated scientists and regulators to develop a wide range of in-vitro, in-silico tools coupled with data science methods. Older drug discovery rules are being constantly modified to churn out any hidden predictive value. Nonetheless, the dose–response concepts remain central to all these methods. Over the last 2 decades medicinal chemists, and pharmacologists have observed that different physicochemical, and pharmacological properties capture trends in toxic responses. We propose that these observations should be viewed in a comprehensive property-response framework where dose is only a factor that modifies the inherent toxicity potential. We then introduce the recently proposed “Drug Toxicity Index (DTI)” and briefly summarize its applications. A webserver is available to calculate DTI values (https://all-tool-kit.github.io/Web-Tool.html).
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Notes
As the human organ and body on-chip systems mature, one can expect age-old ethical questions on what constitutes a living organism can be expected to be raised with these technologies. Thus along with biosafety, ethical aspects should be considered early-on in the development and investment in these technologies alongside, dialogues with regulators, academia, global interest groups, and general public at large.
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VAD conceptualized the perspective, performed literature search and wrote the article. PS contributed by performing literature search and summarizing the FDA, ICH and OECD guidelines in the context of the perspective.
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Dixit, V.A., Singh, P. A property-response perspective on modern toxicity assessment and drug toxicity index (DTI). In Silico Pharmacol. 9, 37 (2021). https://doi.org/10.1007/s40203-021-00096-9
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DOI: https://doi.org/10.1007/s40203-021-00096-9