Phenotypic discovery in AstraZeneca

Tue2  Sep04:00pm(30 mins)
Charter 2


"Phenotypic assays measure the effects, or phenotypes, induced in living cells, tissues or whole organisms by a perturbing agent, such as a natural or synthetic small molecule, peptide, protein, interfering RNA or genetic editing.”
Phenotypic screening is at the core of the discovery of novel targets and relevant drug-like chemical equity with a strong translational link to human pathophysiology, arguably one of the most important challenges in drug discovery. The use of disease relevant cellular models and assays for phenotypic screening has, both internally within AstraZenca and externally, proven to identify compounds and targets associated with a therapeutic premise.
We, in AstraZeneca will drive phenotypic drug discovery by developing novel cellular systems, identifying and validating assay formats enabling a functional read-out of relevance to the disease mechanism of interest and screening high quality libraries of small molecules. To fully capitalize on this effort we will complement it with mechanism of action deconvolution supported by computational chemistry and biology, chemical biology and “omics” profiling technologies.
A key denominator for successful phenotypic screening is the translational link of the in vitro cell systems and assays to eventually mimic the human physiology. This will direct the positive out-come of the phenotypic screen and enable target identification of relevance to drug discovery. We will present how we in AstraZeneca has worked with phenotypic discovery in different areas e.g Neuroscience with ApoE phenotypic screen, Regenerative medicine, Cardiac regeneration Islet Health and finally with identification with factors that differentiate white adipocytes to “brown-ish”.
In the different examples we will describe how we have generated relevant in vitro models and advanced cellular systems utilizing the iPS technology and primary human cells. Recent break-through in the precise genome modification (PGM) area with the CRISPR/Cas9 technology now enables the build of more advanced cell models and will transform the way AstraZeneca delivers reagents and advanced cellular assays. Examples of models generated with this technology will be presented.

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