9O6H

The Structure of PRMT4 in complex with SGC8172

This is a non-PDB format compatible entry.

Summary for 9O6H

• Entry DOI: 10.2210/pdb9o6h/pdb
• Descriptor: Histone-arginine methyltransferase CARM1, 5'-S-(3-{[(4'-chloro[1,1'-biphenyl]-3-yl)methyl]amino}propyl)-5'-thioadenosine (3 entities in total)
• Functional Keywords: prmt4, carm1, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 4
• Total formula weight: 152944.73

Authors

Bush, M.,Noinaj, N.,Huang, R.,Deng, Y. (deposition date: 2025-04-13, release date: 2026-05-13, Last modification date: 2026-05-27)

Primary citation

Kulkarni, A.S.,Deng, Y.,Nam, H.S.,Zhao, T.,Masal, D.P.,Bush, M.M.,Noinaj, N.,Huang, R.
Tailoring PRMT Inhibition: Shifting PRMT7 Selectivity to PRMT4 through "T-Shape" Strategy and "Linker-Specific" Preferences.
J.Med.Chem., 69:9977-9990, 2026

PubMed Abstract: Protein arginine methyltransferases (PRMTs) are appealing therapeutic targets due to their critical roles in regulating numerous cellular processes and their dysregulation in various diseases. Although SAH-based inhibitors effectively target PRMTs, achieving selectivity across different methyltransferases remains a significant challenge. Herein, we employed a hybrid strategy that incorporates optimal linker length and "T-shape" modifications to enhance inhibitor selectivity. Starting with a selective PRMT7 inhibitor SGC8158 (IC <2.5 nM), we successfully transformed it into a selective PRMT4 inhibitor AK442 (IC = 2.6 nM). This approach highlights the potential of these design strategies to tune inhibitor selectivity, facilitating the development of isoform-specific PRMT inhibitors from existing scaffolds.

PubMed: 42066234
DOI: 10.1021/acs.jmedchem.5c01782

Experimental method

X-RAY DIFFRACTION (1.97 Å)