CETSA Explore – a mass spectrometry approach for target deconvolution and compound profiling

Phenotypic drug discovery recently regained popularity owing to its potential for delivering first-in-class treatments for diseases with unmet clinical needs. However, one of the major challenges to phenotypic approaches is the need for target deconvolution and hit confirmation.

CETSA® (Cellular Thermal Shift Assay) Explore is an unbiased mass spectrometry-based, proteome-wide target engagement assessment method for compound profiling measuring not only direct binding but also subsequent downstream pathway events without any label in physiologically relevant conditions.

Helena Almqvist, Project Advisor at Pelago Bioscience will introduce the CETSA® Explore method and also present different applications highlighting how this assay can guide and provide new insights at various stages of drug discovery.

Gizem Akçay, Head of Chemical Biology, Bayer Research and Innovation Center will present how CETSA® Explore was part of a target deconvolution effort following a phenotypic screen. The results were further validated using a targeted CETSA® approach to confirm direct binding.

Key learning objectives

• Advantages of assessing target engagement in physiological conditions, without protein or compound modifications.
• What is CETSA® Explore, an unbiased proteome-wide target engagement assay and how it can accelerate drug discovery programs.
• CETSA® Explore application for target deconvolution and target identification.
• Understanding compound selectivity and Mechanism of Action with CETSA® Explore.
• How CETSA® Navigate – a target CETSA® format can be used for further target engagement validation.

Who should attend?

• Drug discovery researchers
• Chemical biologists
• Scientists working in early drug development, phenotypic screens, and target deconvolution projects.

Presenter: Helen Almqvist (Pelago Bioscience)

Helena Almqvist is a Project Advisor at Pelago Bioscience, where she acts as a scientific liaison for key accounts and develops customized projects. With experience in pre-clinical drug discovery, she joined the company in 2018 to accelerate the CETSA® Navigate HT screening platform and lead CETSA projects tailored to clients. She is an expert in assay development and screening, having worked in small and large pharma settings as well as project management at a national infrastructure. She played a crucial role in adapting the CETSA method for screening and in executing the first CETSA Navigate HT primary screening campaign.

Presenter: Dr. Gizem Akçay (Bayer Research and Innovation Center)

Gizem obtained her PhD in Chemistry from Tufts University and continued her training at Massachusetts Institute of Technology and AstraZeneca R&D Waltham USA. Her work at AstraZeneca led to the discovery of the first covalent Mcl-1 inhibitors, which was recognized as a seminal report in covalent drug discovery. Currently, as the head of Chemical Biology at BAYER Research and Innovation Center, Gizem leads a team focused on technology platforms for drug discovery, including Phenotypic Screens, Target Deconvolution, Chemoproteomics, and new Modalities.

Presenter: Ellie Abbott (SelectScience)

Ellie studied biochemistry at the University of Nottingham, UK, and has previous experience working in management consultancy. As a member of the Editorial team, she now plays an integral role in shaping the content on SelectScience.