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

Article Article scientifique Article Dual Bcl-XL /Bcl-2 inhibitors discovered from DNA-encoded libraries using a fragment pairing strategy eng 2021 author Daguer Jean Pierre 809701 author Gonse Arthur 928290 author Shchukin Yevhenii 910038 author Farrera Soler Lluc 837562 author Barluenga Badiola Sofia 810177 author Winssinger Nicolas 769664 10.1016/j.bmc.2021.116282 0968-0896 https://linkinghub.elsevier.com/retrieve/pii/S096808962100290X 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. Dewey 540 36 Département de chimie organique 141 false Bioorganic & Medicinal Chemistry 44 116282 2372d53e-23f7-4a39-b51d-4463c41f8038 Article (Published version) Public 1-s2.0-S096808962100290X-main.pdf 3372686 application/pdf CC BY-NC-ND openAccess Faculté des sciences / Section de chimie et biochimie / Département de chimie organique

Title	Published in	Access level	OA Policy	Year	Views	Downloads

Dual Bcl-XL /Bcl-2 inhibitors discovered from DNA-encoded libraries using a fragment pairing strategy	Bioorganic & Medicinal Chemistry			2021	249	129

Archive ouverte UNIGE

Shchukin, Yevhenii