Dual Bcl-X<sub>L</sub> /Bcl-2 inhibitors discovered from DNA-encoded libraries using a fragment pairing strategy.

Basic Information

ID: ALA4808196

Journal: Bioorg Med Chem

Title: Dual Bcl-X_L /Bcl-2 inhibitors discovered from DNA-encoded libraries using a fragment pairing strategy.

Authors: Daguer JP, Gonse A, Shchukin Y, Farrera-Soler L, Barluenga S, Winssinger N.

Abstract: A dual Bcl-X_L / 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.

CiteXplore: 34216984

DOI: 10.1016/j.bmc.2021.116282

Patent ID: ┄

Associated Items: Associated Bioactivities Associated Assays Associated Compounds Associated Targets