8DHH
DHODH IN COMPLEX WITH LIGAND 29
Summary for 8DHH
| Entry DOI | 10.2210/pdb8dhh/pdb |
| Descriptor | Dihydroorotate dehydrogenase (quinone), mitochondrial, FLAVIN MONONUCLEOTIDE, OROTIC ACID, ... (8 entities in total) |
| Functional Keywords | dihydroorotate dehydrogenase, dhodh, oxidoreductase, inhibitor, oxidoreductase-inhibitor complex, oxidoreductase/inhibitor |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 41511.27 |
| Authors | Shaffer, P.L. (deposition date: 2022-06-27, release date: 2022-08-17, Last modification date: 2023-10-18) |
| Primary citation | Cisar, J.S.,Pietsch, C.,DeRatt, L.G.,Jacoby, E.,Kazmi, F.,Keohane, C.,Legenski, K.,Matico, R.,Shaffer, P.,Simonnet, Y.,Tanner, A.,Wang, C.Y.,Wang, W.,Attar, R.,Edwards, J.P.,Kuduk, S.D. N -Heterocyclic 3-Pyridyl Carboxamide Inhibitors of DHODH for the Treatment of Acute Myelogenous Leukemia. J.Med.Chem., 65:11241-11256, 2022 Cited by PubMed Abstract: Acute myelogenous leukemia (AML), a disease of the blood and bone marrow, is characterized by the inability of myeloblasts to differentiate into mature cell types. Dihydroorotate dehydrogenase (DHODH) is an enzyme well-known in the pyrimidine biosynthesis pathway; however, small molecule DHODH inhibitors were recently shown to induce differentiation in multiple AML subtypes. Using virtual screening and structure-based drug design approaches, a new series of N-heterocyclic 3-pyridyl carboxamide DHODH inhibitors were discovered. Two lead compounds, and , have potent biochemical and cellular DHODH activity, favorable physicochemical properties, and efficacy in a preclinical model of AML. PubMed: 35925768DOI: 10.1021/acs.jmedchem.2c00788 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.02 Å) |
Structure validation
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