A property-response perspective on modern toxicity assessment and drug toxicity index (DTI).

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).