Exploratory toxicology as an integrated part of drug discovery. Part I: Why and how

Comparison of Drug Metabolism and Its Related Hepatotoxic Effects in HepaRG, Cryopreserved Human Hepatocytes, and HepG2 Cell Cultures

“…1,2) Drug-induced liver injury (DILI) is an example of one of the major toxicity incidences. 3) Therefore, toxicity testing systems for risk assessment of DILI are necessary in the early phase of drug discovery and development for the pharmaceutical industry.…”

REACH and in silico methods: an attractive opportunity for medicinal chemists

“…However, replacing animal testing is a doubleedged sword. On the one hand, it is well known that in vivo experiments are time consuming, expensive and ethically questionable, whereas the use of in vitro and in silico approaches, such as QSARs, can lead to significant savings [5]. On the other hand, the reliability of in silico predictions is often not well documented enough to make safe decisions and justify waiving animal tests.…”

In silico assessment of adverse drug reactions and associated mechanisms

“…Therefore, many serious ADRs can be detected only at the last stages of clinical trials, making ADRs the second most common cause of drug development attrition [3,4]. Clinical trials, in turn, cannot detect all serious ADRs because of limited duration and genetic and nongenetic features of patients who are enrolled in clinical trials (e.g.…”

“…ethnic or disease diversity) [1]. Serious ADRs are often detected only after drug registration and at the beginning of clinical utilization, potentially resulting in thousands of deaths and requiring the withdrawal of the drug from the market [3]. From 1950 to the present day, at least 95 drugs have been withdrawn from local or worldwide markets because of patient deaths [5].…”