6TE1
Structure of the KDM1A/CoREST complex with the inhibitor 2-[3-{4-chloro-3-[(4-chlorophenyl)ethynyl]phenyl}-1-(3-morpholin-4-ylpropyl)-1,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl]-2-oxoethanol
Summary for 6TE1
| Entry DOI | 10.2210/pdb6te1/pdb |
| Descriptor | Lysine-specific histone demethylase 1A, REST corepressor 1, 5-[4-cyclobutyl-1-[2-(4-piperidin-4-yloxyphenoxy)ethyl]imidazol-2-yl]-4-methyl-thieno[3,2-b]pyrrole, ... (6 entities in total) |
| Functional Keywords | histone demethylase, inhibitor, complex, oxidoreductase |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 148312.70 |
| Authors | Pasqualato, S.,Cecatiello, V. (deposition date: 2019-11-11, release date: 2020-06-03, Last modification date: 2024-01-24) |
| Primary citation | Romussi, A.,Cappa, A.,Vianello, P.,Brambillasca, S.,Cera, M.R.,Dal Zuffo, R.,Faga, G.,Fattori, R.,Moretti, L.,Trifiro, P.,Villa, M.,Vultaggio, S.,Cecatiello, V.,Pasqualato, S.,Dondio, G.,So, C.W.E.,Minucci, S.,Sartori, L.,Varasi, M.,Mercurio, C. Discovery of Reversible Inhibitors of KDM1A Efficacious in Acute Myeloid Leukemia Models. Acs Med.Chem.Lett., 11:754-759, 2020 Cited by PubMed Abstract: Lysine-specific demethylase 1 (LSD1 or KDM1A) is a FAD-dependent enzyme that acts as a transcription corepressor or coactivator by regulating the methylation status of histone H3 lysines K4 and K9, respectively. KDM1A represents an attractive target for cancer therapy. While, in the past, the main medicinal chemistry strategy toward KDM1A inhibition was based on the optimization of ligands that irreversibly bind the FAD cofactor within the enzyme catalytic site, we and others have also identified reversible inhibitors. Herein we reported the discovery of 5-imidazolylthieno[3,2-]pyrroles, a new series of KDM1A inhibitors endowed with picomolar inhibitory potency, active in cells and efficacious after oral administration in murine leukemia models. PubMed: 32435381DOI: 10.1021/acsmedchemlett.9b00604 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.11 Å) |
Structure validation
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