9FOC

Crystal structure of the PWWP1 domain of NSD2 bound by compound 11.

This is a non-PDB format compatible entry.

Summary for 9FOC

• Entry DOI: 10.2210/pdb9foc/pdb
• Descriptor: Histone-lysine N-methyltransferase NSD2, (2S)-1-[4-[[(3R)-1,1-bis(oxidanylidene)thiolan-3-yl]methyl-methyl-amino]-6-methyl-pyrimidin-2-yl]-N-methyl-pyrrolidine-2-carboxamide, (2S)-1-[4-[[(3S)-1,1-bis(oxidanylidene)thiolan-3-yl]methyl-methyl-amino]-6-methyl-pyrimidin-2-yl]-N-methyl-pyrrolidine-2-carboxamide, ... (4 entities in total)
• Functional Keywords: drug discovery, nsd2, del, cancer, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 40770.66

Authors

Collie, G.W. (deposition date: 2024-06-11, release date: 2025-09-03, Last modification date: 2025-10-01)

Primary citation

Collie, G.W.,Ackroyd, B.,Corbishley, C.,O'Donovan, D.H.,Edwards, A.,Gohlke, A.,Guo, X.,Howells, B.,Li, Y.,Madin, A.,Milbradt, A.G.,Rivers, E.L.,Talapatra, S.K.,Underwood, E.,Webb, A.
Structural and Molecular Insight into the PWWP1 Domain of NSD2 from the Discovery of Novel Binders Via DNA-Encoded Library Screening.
Acs Med.Chem.Lett., 16:1703-1708, 2025

PubMed 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.

PubMed: 40959233
DOI: 10.1021/acsmedchemlett.5c00396

Experimental method

X-RAY DIFFRACTION (1.618 Å)