6FNH
Crystal Structure of Ephrin A2 (EphA2) Receptor Protein Kinase with a pyrazolo[3,4-d]pyrimidine fragment of NVP-BHG712
Summary for 6FNH
| Entry DOI | 10.2210/pdb6fnh/pdb |
| Descriptor | Ephrin type-A receptor 2, 1-methyl-6-pyridin-3-yl-pyrazolo[3,4-d]pyrimidin-4-amine, 1,2-ETHANEDIOL, ... (4 entities in total) |
| Functional Keywords | inhibitor, complex, protein tyrosine kinase, transferase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 3 |
| Total formula weight | 105122.39 |
| Authors | Kudlinzki, D.,Troester, A.,Witt, K.,Linhard, V.L.,Gande, S.L.,Saxena, K.,Schwalbe, H. (deposition date: 2018-02-04, release date: 2018-08-08, Last modification date: 2024-01-17) |
| Primary citation | Troster, A.,Heinzlmeir, S.,Berger, B.T.,Gande, S.L.,Saxena, K.,Sreeramulu, S.,Linhard, V.,Nasiri, A.H.,Bolte, M.,Muller, S.,Kuster, B.,Medard, G.,Kudlinzki, D.,Schwalbe, H. NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. ChemMedChem, 13:1629-1633, 2018 Cited by PubMed Abstract: Erythropoietin-producing hepatocellular (EPH) receptors are transmembrane receptor tyrosine kinases. Their extracellular domains bind specifically to ephrin A/B ligands, and this binding modulates intracellular kinase activity. EPHs are key players in bidirectional intercellular signaling, controlling cell morphology, adhesion, and migration. They are increasingly recognized as cancer drug targets. We analyzed the binding of NVP-BHG712 (NVP) to EPHA2 and EPHB4. Unexpectedly, all tested commercially available NVP samples turned out to be a regioisomer (NVPiso) of the inhibitor, initially described in a Novartis patent application. They only differ by the localization of a single methyl group on either one of two adjacent nitrogen atoms. The two compounds of identical mass revealed different binding modes. Furthermore, both in vitro and in vivo experiments showed that the isomers differ in their kinase affinity and selectivity. PubMed: 29928781DOI: 10.1002/cmdc.201800398 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.379 Å) |
Structure validation
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