8BDX

Ternary complex between VCB, BRD4-BD2 and PROTAC 48

Summary for 8BDX

• Entry DOI: 10.2210/pdb8bdx/pdb
• Descriptor: Bromodomain-containing protein 4, Elongin-B, Elongin-C, ... (6 entities in total)
• Functional Keywords: protac, degrader, complex, e3 ligase, vhl, vcb, ligase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 8
• Total formula weight: 114722.97

Authors

Sorrell, F.J.,Mueller, J.E.,Lehmann, M.,Wegener, A. (deposition date: 2022-10-20, release date: 2023-02-15, Last modification date: 2024-02-07)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.93 Å)