4C62
Inhibitors of Jak2 Kinase domain
Summary for 4C62
| Entry DOI | 10.2210/pdb4c62/pdb |
| Related | 4C61 |
| Descriptor | TYROSINE-PROTEIN KINASE JAK2, N2-[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]-n4-(1-methylimidazol-4-yl)-6-morpholino-1,3,5-triazine-2,4-diamine, ACETATE ION, ... (4 entities in total) |
| Functional Keywords | transferase |
| Biological source | HOMO SAPIENS (HUMAN) |
| Cellular location | Endomembrane system ; Peripheral membrane protein : O60674 |
| Total number of polymer chains | 2 |
| Total formula weight | 71169.59 |
| Authors | Read, J.,Green, I.,Pollard, H.,Howard, T. (deposition date: 2013-09-17, release date: 2014-01-08, Last modification date: 2024-11-06) |
| Primary citation | Su, Q.,Ioannidis, S.,Chuaqui, C.,Almeida, L.,Alimzhanov, M.,Bebernitz, G.,Bell, K.,Block, M.,Howard, T.,Huang, S.,Huszar, D.,Read, J.A.,Rivard Costa, C.,Shi, J.,Su, M.,Ye, M.,Zinda, M. Discovery of 1-Methyl-1H-Imidazole Derivatives as Potent Jak2 Inhibitors. J.Med.Chem., 57:144-, 2014 Cited by PubMed Abstract: Structure based design, synthesis, and biological evaluation of a novel series of 1-methyl-1H-imidazole, as potent Jak2 inhibitors to modulate the Jak/STAT pathway, are described. Using the C-ring fragment from our first clinical candidate AZD1480 (24), optimization of the series led to the discovery of compound 19a, a potent, orally bioavailable Jak2 inhibitor. Compound 19a displayed a high level of cellular activity in hematopoietic cell lines harboring the V617F mutation and in murine BaF3 TEL-Jak2 cells. Compound 19a demonstrated significant tumor growth inhibition in a UKE-1 xenograft model within a well-tolerated dose range. PubMed: 24359159DOI: 10.1021/JM401546N PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.75 Å) |
Structure validation
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