HTS with micro-fluidic instrument and DNA encoded library. #DEL #HTS #memo

DNA Encoded Library (DEL) is one of powerful tool for HTS. Recently there are many CROs however the approach has limitations. It is limited to affinity-based hit identification. It is difficult to apply insoluble, instable targets. Today I read an interesting article reported by researchers from Roche and Scripps Research Institute. The URL is below.

Activity-Based DNA-Encoded Library Screening

The authors made DEL as ‘One-bead-one-comound’ library and the compounds and beads are linked with photo cleavable linker.

Figure1 in the article shows whole structure of their assay platform. They selected Autotaxin as a screening target. I had an interest in the assay platform. The assay of each compound is performed in a droplet. Laser-induced fluorescence assay detection was used and then hit droplets are separated by difference of voltage AC pulse.

You can see movie of the instrument in supporting information.

They prepared 67100 membered DEL and perform the miniaturized HTS campaign. The throughput of the assay was 30000 beads per hour! And got ~7000 hits with good Z'(0.71).

As a result of the screening the authors get some novel chemical series as hits.

Amazingly, it was required only 8h instrument time and consumed vanishing quantities of activity assay reagents (<10 μg ATX; < 20 nmol substrate) and library (0.0005 total library). Even if huge amount of compounds are assayed.

I think it is difficult to understand the technology from my post. I recommend to read the article.

Integration of cutting edge of science and technology produces new solution for drug discovery. I hope the technology accelerates drug discovery project for human health.

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Published by iwatobipen

I'm medicinal chemist in mid size of pharmaceutical company. I love chemoinfo, cording, organic synthesis, my family.

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