The evolving role of investigative toxicology in the pharmaceutical industry

Weaver, R. J. & Valentin, J. P. Today’s challenges to de-risk and predict drug safety in human “Mind-the-Gap”. Toxicol. Sci. 167, 307–321 (2019).

Article  CAS  PubMed  Google Scholar 

Moggs, J. et al. Investigative safety science as a competitive advantage for Pharma. Expert Opin. Drug Metab. 8, 1071–1082 (2012).

Article  CAS  Google Scholar 

Beilmann, M. et al. Optimizing drug discovery by investigative toxicology: current and future trends. ALTEX 36, 289–313 (2019).

PubMed  Google Scholar 

ICH Topic -M3 (R2): Guidance on Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals (European Medicines Agency, 2009).

Roberts, R. A. Understanding drug targets: no such thing as bad news. Drug Discov. Today 23, 1925–1928 (2018).

Article  PubMed  Google Scholar 

Favuzza, P. et al. Dual plasmepsin-targeting antimalarial agents disrupt multiple stages of the malaria parasite life cycle. Cell Host Microbe 27, 642–658 e612 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zuhl, A. M. et al. Chemoproteomic profiling reveals that cathepsin D off-target activity drives ocular toxicity of beta-secretase inhibitors. Nat. Commun. 7, 13042 (2016).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Barber, J. et al. A target safety assessment of the potential toxicological risks of targeting plasmepsin IX/X for the treatment of malaria. Toxicol. Res. 10, 203–213 (2021).

Article  Google Scholar 

Siintola, E. et al. Cathepsin D deficiency underlies congenital human neuronal ceroid-lipofuscinosis. Brain 129, 1438–1445 (2006).

Article  PubMed  Google Scholar 

Ramirez-Montealegre, D., Rothberg, P. G. & Pearce, D. A. Another disorder finds its gene. Brain 129, 1353–1356 (2006).

Article  PubMed  Google Scholar 

Hornberg, J. J. et al. Exploratory toxicology as an integrated part of drug discovery. Part II: screening strategies. Drug Discov. Today 19, 1137–1144 (2014).

Article  CAS  PubMed  Google Scholar 

Hornberg, J. J. et al. Exploratory toxicology as an integrated part of drug discovery. Part I: why and how. Drug Discov. Today 19, 1131–1136 (2014).

Article  CAS  PubMed  Google Scholar 

Atienzar, F. A. et al. Predictivity of dog co-culture model, primary human hepatocytes and HepG2 cells for the detection of hepatotoxic drugs in humans. Toxicol. Appl. Pharm. 275, 44–61 (2014).

Article  CAS  Google Scholar 

Atienzar, F. et al. Investigative safety strategies to improve success in drug development. J. Med. Dev. Sci. 2, 2–29 (2016).

Article  Google Scholar 

Lin, Z. W. & Will, Y. Evaluation of drugs with specific organ toxicities in organ-specific cell lines. Toxicol. Sci. 126, 114–127 (2012).

Article  CAS  PubMed  Google Scholar 

Langhans, S. A. Three-dimensional in vitro cell culture models in drug discovery and drug repositioning. Front. Pharmacol. 9, 6 (2018).

Article  PubMed  PubMed Central  Google Scholar 

Low, L. A., Mummery, C., Berridge, B. R., Austin, C. P. & Tagle, D. A. Organs-on-chips: into the next decade. Nat. Rev. Drug Discov. 20, 345–361 (2021).

Article  CAS  PubMed  Google Scholar 

Natale, A. et al. Technological advancements for the development of stem cell-based models for hepatotoxicity testing. Arch. Toxicol. 93, 1789–1805 (2019).

Article  CAS  PubMed  Google Scholar 

Baudy, A. R. et al. Liver microphysiological systems development guidelines for safety risk assessment in the pharmaceutical industry. Lab Chip 20, 215–225 (2020).

Article  CAS  PubMed  Google Scholar 

Vulto, P. & Joore, J. Adoption of organ-on-chip platforms by the pharmaceutical industry. Nat. Rev. Drug Discov. 20, 961–962 (2021).

Article  CAS  PubMed  Google Scholar 

McAleer, C. W. et al. On the potential of in vitro organ-chip models to define temporal pharmacokinetic-pharmacodynamic relationships. Sci. Rep. 9, 9619 (2019).

Article  PubMed  PubMed Central  Google Scholar 

Vo, A. H., Van Vleet, T. R., Gupta, R. R., Liguori, M. J. & Rao, M. S. An overview of machine learning and big data for drug toxicity evaluation. Chem. Res. Toxicol. 33, 20–37 (2020).

Article  CAS  PubMed  Google Scholar 

Hunter, F. M. I. et al. Drug safety data curation and modeling in ChEMBL: boxed warnings and withdrawn drugs. Chem. Res. Toxicol. 34, 385–395 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ferreira, S. et al. Quantitative systems toxicology modeling to address key safety questions in drug development: a focus of the TransQST consortium. Chem. Res. Toxicol. 33, 7–9 (2020).

Article  CAS  PubMed  Google Scholar 

Weaver, R. J. et al. Test systems in drug discovery for hazard identification and risk assessment of human drug-induced liver injury. Expert. Opin. Drug Met. 13, 767–782 (2017).

Article  CAS  Google Scholar 

Atienzar, F. A. et al. Key challenges and opportunities associated with the use of in vitro models to detect human DILI: integrated risk assessment and mitigation plans. Biomed. Res. Int. 2016, 9737820 (2016).

Article  Google Scholar 

Bell, C. C. et al. Transcriptional, functional, and mechanistic comparisons of stem cell-derived hepatocytes, HepaRG cells, and three-dimensional human hepatocyte spheroids as predictive in vitro systems for drug-induced liver injury. Drug Metab. Dispos. 45, 419–429 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hart, S. N. et al. A comparison of whole genome gene expression profiles of HepaRG cells and HepG2 cells to primary human hepatocytes and human liver tissues. Drug Metab. Dispos. 38, 988–994 (2010).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rogue, A., Lambert, C., Spire, C., Claude, N. & Guillouzo, A. Interindividual variability in gene expression profiles in human hepatocytes and comparison with HepaRG cells. Drug Metab. Dispos. 40, 151–158 (2012).

Article  CAS  PubMed  Google Scholar 

Castell, J. V., Jover, R., Martinez-Jimenez, C. P. & Gomez-Lechon, M. J. Hepatocyte cell lines: their use, scope and limitations in drug metabolism studies. Expert. Opin. Drug Met. 2, 183–212 (2006).

Article  CAS  Google Scholar 

Sison-Young, R. L. et al. A multicenter assessment of single-cell models aligned to standard measures of cell health for prediction of acute hepatotoxicity. Arch. Toxicol. 91, 1385–1400 (2017).

Article  CAS  PubMed  Google Scholar 

Kamalian, L. et al. The utility of HepG2 cells to identify direct mitochondrial dysfunction in the absence of cell death. Toxicol. Vitr. 29, 732–740 (2015).

Article  CAS  Google Scholar 

Jang, K. J. et al. Reproducing human and cross-species drug toxicities using a Liver-Chip. Sci. Transl. Med. 11, eaax5516 (2019).

Article  CAS  PubMed  Google Scholar 

Proctor, W. R. et al. Utility of spherical human liver microtissues for prediction of clinical drug-induced liver injury. Arch. Toxicol. 91, 2849–2863 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Whitebread, S. et al. Secondary pharmacology: screening and interpretation of off-target activities - focus on translation. Drug Discov. Today 21, 1232–1242 (2016).

Article  CAS  PubMed  Google Scholar 

Whitebread, S., Hamon, J., Bojanic, D. & Urban, L. Keynote review: in vitro safety pharmacology profiling: an essential tool for successful drug development. Drug Discov. Today 10, 1421–1433 (2005).

Article  CAS  PubMed  Google Scholar 

Bowes, J. et al. Reducing safety-related drug attrition: the use of in vitro pharmacological profiling. Nat. Rev. Drug Discov. 11, 909–922 (2012).

Article  CAS  PubMed  Google Scholar 

Valentin, J. P. et al. In vitro secondary pharmacological profiling: an IQ-DruSafe industry survey on current practices. J. Pharmacol. Toxicol. Methods 93, 7–14 (2018).

Article  CAS  PubMed  Google Scholar 

Jenkinson, S., Schmidt, F., Rosenbrier Ribeiro, L., Delaunois, A. & Valentin, J. P. A practical guide to secondary pharmacology in drug discovery. J. Pharmacol. Toxicol. Methods 105, 106869 (2020).

Article  CAS  PubMed  Google Scholar 

Hughes, J. D. et al. Physiochemical drug properties associated with in vivo toxicological outcomes. Bioorg. Med. Chem. Lett. 18, 4872–4875 (2008).

Article  CAS 

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