8BDJ

VCB in complex with compound 30

8BDJ の概要

• エントリーDOI: 10.2210/pdb8bdj/pdb
• 分子名称: Elongin-B, Elongin-C, von Hippel-Lindau disease tumor suppressor, ... (6 entities in total)
• 機能のキーワード: protac, degrader, complex, e3 ligase, vhl, vcb, ligase, vh032
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 168253.19

構造登録者

Sorrell, F.J.,Mueller, J.E.,Lehmann, M.,Wegener, A. (登録日: 2022-10-19, 公開日: 2023-02-15, 最終更新日: 2024-10-09)

主引用文献

Krieger, J.,Sorrell, F.J.,Wegener, A.A.,Leuthner, B.,Machrouhi-Porcher, F.,Hecht, M.,Leibrock, E.M.,Muller, J.E.,Eisert, J.,Hartung, I.V.,Schlesiger, S.
Systematic Potency and Property Assessment of VHL Ligands and Implications on PROTAC Design.
Chemmedchem, 18:e202200615-e202200615, 2023

PubMed Abstract: Herein, we describe a systematic SAR- and SPR-investigation of the peptidomimetic hydroxy-proline based VHL-ligand VH032, from which most to-date published VHL-targeting PROTACs have been derived. This study provides for the first time a consistent data set which allows for direct comparison of structural variations including those which were so far hidden in patent literature. The gained knowledge about improved VHL binders was used to design a small library of highly potent BRD4-degraders comprising different VHL exit vectors. Newly designed degraders showed favorable molecular properties and significantly improved degradation potency compared to MZ1.

PubMed: 36749883
DOI: 10.1002/cmdc.202200615

実験手法

X-RAY DIFFRACTION (2.02 Å)