9ZL2
Crystal structure of PRMT5:MEP50 in complex with MTA and oxamide compound 8
This is a non-PDB format compatible entry.
Summary for 9ZL2
| Entry DOI | 10.2210/pdb9zl2/pdb |
| Descriptor | Protein arginine N-methyltransferase 5, Methylosome protein 50, 5'-DEOXY-5'-METHYLTHIOADENOSINE, ... (6 entities in total) |
| Functional Keywords | methyltransferase, sam, mtap-null, mta-cooperative, transferase, transferase-inhibitor complex, transferase/inhibitor |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 112403.88 |
| Authors | |
| Primary citation | Cottrell, K.M.,Briggs, K.J.,Tsai, A.,Liang, C.,McCarren, P.,Whittington, D.A.,Zhang, M.,Zhang, W.,Huang, A.,Andersen, J.,Maxwell, J.P. The Discovery of TNG456: A Highly Potent, Selective, Brain-Penetrant MTA-Cooperative PRMT5 Inhibitor for the Treatment of MTAP -Deleted Cancers. J.Med.Chem., 2026 Cited by PubMed Abstract: Homozygous deletion of the methylthioadenosine phosphorylase () gene occurs in 10-15% of all human cancers and up to 50% of high-grade malignant gliomas, representing one of the largest opportunities for precision oncology. Loss of MTAP leads to the accumulation of 5'-methylthioadenosine (MTA), which sensitizes tumor cells to inhibition of protein arginine methyltransferase 5 (PRMT5). Herein we describe the discovery of , a potent and highly selective MTA-cooperative PRMT5 inhibitor that is brain penetrant in preclinical species and currently in Phase I/II clinical studies for the treatment of advanced or metastatic solid tumors with MTAP loss, with a focus on glioblastoma. PubMed: 42150143DOI: 10.1021/acs.jmedchem.6c00035 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.18 Å) |
Structure validation
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