5DHJ
PIM1 in complex with Cpd4 (3-methyl-5-(pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine)
Summary for 5DHJ
| Entry DOI | 10.2210/pdb5dhj/pdb |
| Related | 5DGZ 5DIA |
| Descriptor | Serine/threonine-protein kinase pim-1, 3-methyl-5-(pyridin-3-yl)-2H-pyrazolo[3,4-c]pyridine, PHOSPHATE ION, ... (4 entities in total) |
| Functional Keywords | pim-1, kinase, atp-competitive, structure-based drug design, transferase-transferase inhibitor complex, transferase/transferase inhibitor |
| Biological source | Homo sapiens (Human) |
| Cellular location | Isoform 2: Cytoplasm. Isoform 1: Cell membrane: P11309 |
| Total number of polymer chains | 1 |
| Total formula weight | 34847.32 |
| Authors | Murray, J.M.,Wallweber, H. (deposition date: 2015-08-31, release date: 2015-10-28, Last modification date: 2024-03-06) |
| Primary citation | Hu, H.,Wang, X.,Chan, G.K.,Chang, J.H.,Do, S.,Drummond, J.,Ebens, A.,Lee, W.,Ly, J.,Lyssikatos, J.P.,Murray, J.,Moffat, J.G.,Chao, Q.,Tsui, V.,Wallweber, H.,Kolesnikov, A. Discovery of 3,5-substituted 6-azaindazoles as potent pan-Pim inhibitors. Bioorg.Med.Chem.Lett., 25:5258-5264, 2015 Cited by PubMed Abstract: Pim kinase inhibitors are promising cancer therapeutics. Pim-2, among the three Pim isoforms, plays a critical role in multiple myeloma yet inhibition of Pim-2 is challenging due to its high affinity for ATP. A co-crystal structure of a screening hit 1 bound to Pim-1 kinase revealed the key binding interactions of its indazole core within the ATP binding site. Screening of analogous core fragments afforded 1H-pyrazolo[3,4-c]pyridine (6-azaindazole) as a core for the development of pan-Pim inhibitors. Fragment and structure based drug design led to identification of the series with picomolar biochemical potency against all three Pim isoforms. Desirable cellular potency was also achieved. PubMed: 26459208DOI: 10.1016/j.bmcl.2015.09.052 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.457 Å) |
Structure validation
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