6DI1
CRYSTAL STRUCTURE OF BTK IN COMPLEX WITH COVALENT FRAGMENT LIGAND
Summary for 6DI1
| Entry DOI | 10.2210/pdb6di1/pdb |
| Related | 6di0 |
| Descriptor | Tyrosine-protein kinase BTK, 4-amino-2-[(3S)-3-(propanoylamino)pyrrolidin-1-yl]pyrimidine-5-carboxamide (3 entities in total) |
| Functional Keywords | lead optimization, fragment screening by x-ray, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor |
| Biological source | Homo sapiens |
| Total number of polymer chains | 1 |
| Total formula weight | 31876.60 |
| Authors | Jiang, X. (deposition date: 2018-05-22, release date: 2018-10-17, Last modification date: 2024-11-20) |
| Primary citation | Caldwell, R.,Liu-Bujalski, L.,Qiu, H.,Mochalkin, I.,Jones, R.,Neagu, C.,Goutopoulos, A.,Grenningloh, R.,Johnson, T.,Sherer, B.,Gardberg, A.,Follis, A.V.,Morandi, F.,Head, J. Discovery of a novel series of pyridine and pyrimidine carboxamides as potent and selective covalent inhibitors of Btk. Bioorg. Med. Chem. Lett., 28:3419-3424, 2018 Cited by PubMed Abstract: Btk is an attractive target for the treatment of a range of Bcell malignancies as well as several autoimmune diseases such as murine lupus and rheumatoid arthritis. Several covalent irreversible inhibitors of Btk are currently in development including ibrutinib which was approved for treatment of B-cell malignancies. Herein, we describe our efforts using X-ray guided structure based design (SBD) to identify a novel chemical series of covalent Btk inhibitors. The resulting pyridine carboxamides were potent and selective inhibitors of Btk having excellent enzymatic and cellular inhibitory activity. PubMed: 30290988DOI: 10.1016/j.bmcl.2018.09.033 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.1 Å) |
Structure validation
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