Challenges in Assessing Mitochondrial Toxicities and Liabilities in Drug Discovery

Being able to identify compounds that induce toxicities is an important part of lead-optimization during drug discovery.

Cell-based assays, such as the glucose-galactose switch assay, are commonly employed in the discovery space. However, these assays lack a depth of sensitivity that is crucial in capturing many mitochondrial toxic compounds that can appear in late stage failures.

As such, assays that collect direct measurements of drug-related effects on mitochondrial respiration have gained interest from industry due to their increased sensitivity.

We will outline the thresholding and other qualification measures we employ to the MitoXpress Xtra Oxygen Consumption assay and to the Agilent Seahorse XFe96 analyzer with the Cell Mito Stress Test. We will then share how this data, in addition to data from respiration studies using isolated rat liver mitochondria, informs preclinical risk assessment.

In this eSeminar we will discuss:

  • Solutions with direct measurements of mitochondrial function that allow for the highest level of sensitivity in detecting mitochondrial toxicities 
  • How Genentech employs these assays to support small-molecule lead optimization and issue mitigation
  • A cross comparison of popular assays using a test set of commercial drugs with known clinical toxicities

For Research Use Only.  Not for use in diagnostic procedures.

Wednesday, November 14, 2018
9:00 PST (Los Angeles)
12:00 EST (New York)

17:00 GMT (London)

Available On Demand after November 14
All registrants will be notified when available

Presented by:
Tomomi Kiyota, PhD
Scientist, Investigative Toxicology, Safety Assessment,
Genentech, Inc.

William Proctor, PhD
DABT, Associate Director/Senior Scientist, Investigative Toxicology, Safety Assessment,
Genentech, Inc.

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