As shown previously by AstraZeneca in Nature reviews*, one third of the safety failures is linked to CNS (central nervous system) toxicity observed during the clinical trials.

_Toxiclogy_organs

* Cook D, Brown D, Alexander R, March R, Morgan P, Satterthwaite G, Pangalos MN (2014) Lessons learned from the fate of AstraZeneca’s drug pipeline: a five-dimensional framework. Nat Rev Drug Discov. 13(6):419-31.

To avoid this attrition, the potential neurotoxicity of new chemical entities should be checked as soon as possible during the drug discovery process

To learn more on these assays, please refer to our posters that have been presented in different congresses:

Neurotoxicity assay on SH-SY5Y

Study of compounds toxicity on neurons

This assay can be performed by cell imaging in HCA/HCS on brain cells, including neuronal cell lines like SH-SY5Y. Neurotoxicity assays are performed by treating neuronal cells during at least 48h with the tested compounds.

Requirements

  • Compounds: powder or stock solution
  • Cells:  differentiated neuroblastoma SH-SY5Y cell line
  • Plate format: 96 or 384-well plates

Example of Rotenone

Differentiated SH-SY5Y cells were exposed to increasing concentrations of rotenone

Impaired communication between neurons can occur by the loss of neurites at lower doses than neuronal cell death.

Don’t hesitate to ask for our short report on SH-SY5Y cells exposed to our in–house neurotoxicity library !