CETSA® can determine cellular target engagement in physiologically relevant settings of the native, full-length protein and can potentially unlock novel chemical space. CETSA® library screening in intact cells gives direct confirmation on target engagement of your library compounds in physiological conditions from the onset.
The high-throughput CETSA® format, known as CETSA® Navigate HT, is based on dual-antibody proximity detection systems suitable for miniaturization in 384 and 1536 microtiter plates. Subsequently, the CETSA® Navigate HT format enables rapid screening of compound libraries. Almqvist et al. reported on the first use of CETSA® Navigate HT for screening of a compound library of more than 10K structurally diverse compounds against the therapeutically relevant protein target thymidylate synthase (TS). AstraZeneca recently reported on the use of CETSA® Navigate HT for primary screening of a 500K compound large library against the validated oncology target CRAF. The CETSA® Navigate HT format has proven to be robust, with low liability towards PAINS and, thus, to be a reliable tool for screening of both large and focused libraries for identifying new chemical starting points.
Almqvist H, Axelssson H, Rozbeh J, Dan C, Mateus A, Haraldsson M, Larsson A, Martinez Molina D, Artursson P, Lundbäck T, Nordlund P. CETSA screening identifies known and novel thymidylate synthase inhibitors and slow intracellular activation of 5-fluorouracil. (2016) Nature Communications 7:11040
Shaw J, Dale I, Hemsley P, Leach L, et al. Positioning High-Throughput CETSA in Early Drug Discovery through Screening against B-Raf and PARP1. (2019) SLAS Discov. DOI: 10.1177/2472555218813332