These are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information. For more information, please see our FAQs.
2 files

Discovery of an Unexpected Similarity in Ligand Binding Between BRD4 and PPARγ

submitted on 29.12.2019, 21:36 and posted on 31.12.2019, 09:11 by Lina Humbeck, Jette Pretzel, Saskia Spitzer, Oliver Koch
Knowledge about interrelationships between different proteins is crucial in fundamental research for the elucidation of protein networks and pathways. Furthermore, it is especially critical in chemical biology to identify further key regulators of a disease and to take advantage of polypharmacology effects. A comprehensive scaffold-based analysis uncovered an unexpected relationship between bromodomain-containing protein 4 (BRD4) and peroxisome-proliferator activated receptor gamma (PPARγ). They are both important drug targets for cancer therapy and many more important diseases. Both proteins share binding site similarities near a common hydrophobic subpocket which should allow the design of a polypharmacology-based ligand targeting both proteins. Such a dual-BRD4-PPARγ-modulator could show synergistic effects with a higher efficacy or delayed resistance development in, for example, cancer therapy. Thereon, a complex structure of sulfasalazine was obtained that involves two bromodomains and could be a potential starting point for the design of a bivalent BRD4 inhibitor.


DFG - SPP 1736 - Algorithms for Big Data - KO 4689/2-1

BMBF - Grant No. 1316053


Email Address of Submitting Author


TU Dortmund University



ORCID For Submitting Author


Declaration of Conflict of Interest

The authors declare no conflict of interest.