Safety

Manually-curated safety data to support target prioritisation

Overview

Throughout the drug discovery and development process, target safety assessments help with understanding the role of the drug target in normal physiology and potential unintended adverse consequences and safety liabilities when modulating the target with a chemical compound or drug (Brennan, 2017).

To support target prioritisation, we have manually curated experimental data and insights from publications and other well-known sources of target safety and toxicity data, including Tox21 and eTox.

Safety data is available on the target profile page and is broken down into three categories:

  • Known side effects: information on safety liabilities based on dosing responses in organs and systems when activating and/or inhibiting a target

  • Safety risk: information on safety liabilities and hepatic and cardiac toxicity

  • Non-clinical experimental toxicity: information on the routine testing and screening of targets in non-clinical experimental toxicity panels.

Computational pipelines and datasets

Target safety datasets are mapped to the correct Ensembl gene ID and ingested during our initial pipeline steps. The files are available for download from our data download page.

Publications

Bowes J, Brown AJ, Hamon J, Jarolimek W, Sridhar A, Waldron G, Whitebread S. Reducing safety-related drug attrition: the use of in vitro pharmacological profiling. Nat Rev Drug Discov. 2012 Dec;11(12):909-22. doi: 10.1038/nrd3845. PMID: 23197038.

Brennan R.J. (2017) Target Safety Assessment: Strategies and Resources. In: Gautier JC. (eds) Drug Safety Evaluation. Methods in Molecular Biology, vol 1641. Humana Press, New York, NY. doi: 10.1007/978-1-4939-7172-5_12

Cases M, Briggs K, Steger-Hartmann T, Pognan F, Marc P, Kleinöder T, Schwab CH, Pastor M, Wichard J, Sanz F. The eTOX data-sharing project to advance in silico drug-induced toxicity prediction. Int J Mol Sci. 2014 Nov 14;15(11):21136-54. doi: 10.3390/ijms151121136. PMID: 25405742; PMCID: PMC4264217.

Force T, Kolaja KL. Cardiotoxicity of kinase inhibitors: the prediction and translation of preclinical models to clinical outcomes. Nat Rev Drug Discov. 2011 Feb;10(2):111-26. doi: 10.1038/nrd3252. PMID: 21283106.

Krewski D, Acosta D Jr, Andersen M, Anderson H, Bailar JC 3rd, Boekelheide K, Brent R, Charnley G, Cheung VG, Green S Jr, Kelsey KT, Kerkvliet NI, Li AA, McCray L, Meyer O, Patterson RD, Pennie W, Scala RA, Solomon GM, Stephens M, Yager J, Zeise L. Toxicity testing in the 21st century: a vision and a strategy. J Toxicol Environ Health B Crit Rev. 2010 Feb;13(2-4):51-138. doi: 10.1080/10937404.2010.483176. PMID: 20574894; PMCID: PMC4410863.

Lamore SD, Ahlberg E, Boyer S, Lamb ML, Hortigon-Vinagre MP, Rodriguez V, Smith GL, Sagemark J, Carlsson L, Bates SM, Choy AL, Stålring J, Scott CW, Peters MF. Deconvoluting Kinase Inhibitor Induced Cardiotoxicity. Toxicol Sci. 2017 Jul 1;158(1):213-226. doi: 10.1093/toxsci/kfx082. PMID: 28453775; PMCID: PMC5837613.

Lynch JJ 3rd, Van Vleet TR, Mittelstadt SW, Blomme EAG. Potential functional and pathological side effects related to off-target pharmacological activity. J Pharmacol Toxicol Methods. 2017 Sep;87:108-126. doi: 10.1016/j.vascn.2017.02.020. PMID: 28216264.

Urban L, Whitebread S, Hamon J et al. Screening for safety-relevant off-target affinities. In: Polypharmacology in Drug Discovery. Peters JU (Ed.). John Wiley and Sons, NJ, USA (2012). doi: 10.1002/9781118098141.ch2.