Structural and Molecular Insight into the PWWP1 Domain of NSD2 from the Discovery of Novel Binders Via DNA-Encoded Library Screening
Year: 2025
Type: article
Abstract: NSD2 is a key epigenetic regulator and has received considerable attention as a drug target due to its well-documented role in tumorigenesis. We report here a DNA-encoded library screen targeting the PWWP1 domain of NSD2 from which we discovered novel, potent, and selective binders. Furthermore, these compounds were used to develop a novel crystal system, increasing our understanding of the folding of this domain. Together, these results provide a solid molecular and structural basis for the further study of the PWWP1 domain of NSD2 as a cancer drug target.
Source: ACS Medicinal Chemistry Letters
Authors: Gavin W. Collie, Bryony Ackroyd, Catriona Corbishley, Daniel H. O’Donovan, Alex Edwards, Andrea Gohlke, Xiaoxiao Guo, Bethan Howells, Yuliang Li, Andrew Madin, Alexander G. Milbradt, Emma L. Rivers, Sandeep K. Talapatra, Elizabeth Underwood, Alice Webb
Institutions: AstraZeneca (United Kingdom), Pharmaron (China)
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
OpenAlex ID: W4413534009