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Scientific article
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English

Dual Bcl-XL /Bcl-2 inhibitors discovered from DNA-encoded libraries using a fragment pairing strategy

Published inBioorganic & Medicinal Chemistry, vol. 44, no. 116282
Publication date2021
Abstract

A dual Bcl-XL / Bcl-2 inhibitor was discovered from DNA-encoded libraries using a two steps process. In the first step, DNA was used to pair PNA-encoded fragments exploring > 250 000 combinations. In the second step, a focused library combining the selected fragments with linkers of different lengths and geometries led to the identification of tight binding adducts that were further investigated for their selective target engagement in pull-down assays, for their affinity by SPR, and their selectivity in a cytotoxicity assay. The best compound showed comparable cellular activity to venetoclax, the first-in-class therapeutic targeting Bcl-2.

Citation (ISO format)
DAGUER, Jean Pierre et al. Dual Bcl-XL /Bcl-2 inhibitors discovered from DNA-encoded libraries using a fragment pairing strategy. In: Bioorganic & Medicinal Chemistry, 2021, vol. 44, n° 116282. doi: 10.1016/j.bmc.2021.116282
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ISSN of the journal0968-0896
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Technical informations

Creation07/05/2021 9:29:00 AM
First validation07/05/2021 9:29:00 AM
Update time03/16/2023 12:50:39 AM
Status update03/16/2023 12:50:38 AM
Last indexation02/12/2024 1:28:02 PM
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