9N3O
Crystal structure of PRMT5:MEP50 in complex with MTA and oxamide compound 14
This is a non-PDB format compatible entry.
Summary for 9N3O
| Entry DOI | 10.2210/pdb9n3o/pdb |
| Descriptor | Protein arginine N-methyltransferase 5, Methylosome protein 50, 5'-DEOXY-5'-METHYLTHIOADENOSINE, ... (8 entities in total) |
| Functional Keywords | inhibitor, mta-cooperative, mtap-null, transferase, transferase-inhibitor complex, transferase/inhibitor |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 113142.55 |
| Authors | Whittington, D.A. (deposition date: 2025-01-31, release date: 2025-03-12, Last modification date: 2025-03-19) |
| Primary citation | Cottrell, K.M.,Briggs, K.J.,Tsai, A.,Tonini, M.R.,Whittington, D.A.,Gong, S.,Liang, C.,McCarren, P.,Zhang, M.,Zhang, W.,Huang, A.,Maxwell, J.P. Discovery of TNG462: A Highly Potent and Selective MTA-Cooperative PRMT5 Inhibitor to Target Cancers with MTAP Deletion. J.Med.Chem., 68:5097-5119, 2025 Cited by PubMed Abstract: The gene encoding for MTAP is one of the most commonly deleted genes in cancer, occurring in approximately 10-15% of all human cancer. We have previously described the discovery of TNG908, a brain-penetrant clinical-stage compound that selectively targets -deleted cancer cells by binding to and inhibiting PRMT5 cooperatively with MTA, which is present in elevated concentrations in -deleted cells. Herein we describe the discovery of TNG462, a more potent and selective MTA-cooperative PRMT5 inhibitor with improved DMPK properties that is selective for -deleted cancers and is currently in Phase I/II clinical trials. PubMed: 40035511DOI: 10.1021/acs.jmedchem.4c03067 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.37 Å) |
Structure validation
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