Loading
PDBj
MenuPDBj@FacebookPDBj@X(formerly Twitter)PDBj@BlueSkyPDBj@YouTubewwPDB FoundationwwPDBDonate
RCSB PDBPDBeBMRBAdv. SearchSearch help

8G3C

Crystal structure of human WDR5 in complex with N-[(2'-cyano[1,1'-biphenyl]-4-yl)methyl]-3-hydroxy-6-methyl-4-oxo-4H-pyran-2-carboxamide (compound 1, WDR5-MYC PPI inhibitor)

Summary for 8G3C
Entry DOI10.2210/pdb8g3c/pdb
DescriptorWD repeat-containing protein 5, N-[(2'-cyano[1,1'-biphenyl]-4-yl)methyl]-3-hydroxy-6-methyl-4-oxo-4H-pyran-2-carboxamide (3 entities in total)
Functional Keywordswdr5, wbm, myc, small molecule, oncoprotein-inhibitor complex, oncoprotein/inhibitor
Biological sourceHomo sapiens (human)
Total number of polymer chains1
Total formula weight34751.35
Authors
Zhao, M. (deposition date: 2023-02-07, release date: 2023-06-28, Last modification date: 2023-10-25)
Primary citationDing, J.,Liu, L.,Chiang, Y.L.,Zhao, M.,Liu, H.,Yang, F.,Shen, L.,Lin, Y.,Deng, H.,Gao, J.,Sage, D.R.,West, L.,Llamas, L.A.,Hao, X.,Kawatkar, S.,Li, E.,Jain, R.K.,Tallarico, J.A.,Canham, S.M.,Wang, H.
Discovery and Structure-Based Design of Inhibitors of the WD Repeat-Containing Protein 5 (WDR5)-MYC Interaction.
J.Med.Chem., 66:8310-8323, 2023
Cited by
PubMed Abstract: WDR5 is a critical chromatin cofactor of MYC. WDR5 interacts with MYC through the WBM pocket and is hypothesized to anchor MYC to chromatin through its WIN site. Blocking the interaction of WDR5 and MYC impairs the recruitment of MYC to its target genes and disrupts the oncogenic function of MYC in cancer development, thus providing a promising strategy for the treatment of MYC-dysregulated cancers. Here, we describe the discovery of novel WDR5 WBM pocket antagonists containing a 1-phenyl dihydropyridazinone 3-carboxamide core that was identified from high-throughput screening and subsequent structure-based design. The leading compounds showed sub-micromolar inhibition in the biochemical assay. Among them, compound can disrupt WDR5-MYC interaction in cells and reduce MYC target gene expression. Our work provides useful probes to study WDR5-MYC interaction and its function in cancers, which can also be used as the starting point for further optimization toward drug-like small molecules.
PubMed: 37307526
DOI: 10.1021/acs.jmedchem.3c00787
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (1.8 Å)
Structure validation

239803

건을2025-08-06부터공개중

PDB statisticsPDBj update infoContact PDBjnumon