Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Aug 12;64(15):10680-10681.
doi: 10.1021/acs.jmedchem.1c01126. Epub 2021 Jul 23.

The Future of Medicinal Chemistry, PROTAC, and Undruggable Drug Targets

Antti Poso  1   2
Affiliations

The Future of Medicinal Chemistry, PROTAC, and Undruggable Drug Targets

Antti Poso. J Med Chem. .

Abstract

WRD5 is a promising target for anticancer drug discovery. In addition, it plays a vital role in epigenetic regulation. Since biological inactivation of WRD5 is difficult to reach via classical approach, PROTACs (Proteolysis Targeting Chimeras) are offering a new option. In a study, published in this journal, new WRD5 targeting PROTACS are introduced. These new compounds, which are also active in cells, make it possible to evaluate the value of WRD5 as a drug target.

PubMed Disclaimer

Conflict of interest statement

The author declares no competing financial interests

Figures

Figure 1
Figure 1
Schematic representation of the designed PROTACs. New compounds were able to cross the cell membrane and achieve biologically relevant WDR5 degradation. VHL structure 4W9H, and WDR5 structure 4QL1.
See this image and copyright information in PMC

References

    1. Mullard A. Amgen Overcomes Historically Undruggable Target, with FDA Nod for First KRAS Inhibitor. Nat. Rev. Drug Discovery 2021, 20, 496.10.1038/d41573-021-00098-4. - DOI - PubMed
    1. Getlik M.; Smil D.; Zepeda-Velázquez C.; Bolshan Y.; Poda G.; Wu H.; Dong A.; Kuznetsova E.; Marcellus R.; Senisterra G.; Dombrovski L.; Hajian T.; Kiyota T.; Schapira M.; Arrowsmith C. H.; Brown P. J.; Vedadi M.; Al-awar R. Structure-Based Optimization of a Small Molecule Antagonist of the Interaction Between WD Repeat-Containing Protein 5 (WDR5) and Mixed-Lineage Leukemia 1 (MLL1). J. Med. Chem. 2016, 59 (6), 2478–2496. 10.1021/acs.jmedchem.5b01630. - DOI - PubMed

MeSH terms