8E2M
Bruton's tyrosine kinase (BTK) with compound 13
Summary for 8E2M
| Entry DOI | 10.2210/pdb8e2m/pdb |
| Descriptor | Tyrosine-protein kinase BTK, (5P)-5-[4-methyl-6-(2-methylpropyl)pyridin-3-yl]-4-oxo-N-[(1R,2S)-2-propanamidocyclopentyl]-4,5-dihydro-3H-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide, TRIETHYLENE GLYCOL, ... (4 entities in total) |
| Functional Keywords | protein kinase, inhibitor, covalent, transferase-transferase inhibitor complex, transferase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 32269.11 |
| Authors | Alexander, R.,Milligan, C.M. (deposition date: 2022-08-15, release date: 2022-11-16, Last modification date: 2024-10-16) |
| Primary citation | Tichenor, M.S.,Wiener, J.J.M.,Rao, N.L.,Bacani, G.M.,Wei, J.,Pooley Deckhut, C.,Barbay, J.K.,Kreutter, K.D.,Chang, L.,Clancy, K.W.,Murrey, H.E.,Wang, W.,Ahn, K.,Huber, M.,Rex, E.,Coe, K.J.,Wu, J.,Rui, H.,Sepassi, K.,Gaudiano, M.,Bekkers, M.,Cornelissen, I.,Packman, K.,Seierstad, M.,Xiouras, C.,Bembenek, S.D.,Alexander, R.,Milligan, C.,Balasubramanian, S.,Lebsack, A.D.,Venable, J.D.,Philippar, U.,Edwards, J.P.,Hirst, G. Discovery of JNJ-64264681: A Potent and Selective Covalent Inhibitor of Bruton's Tyrosine Kinase. J.Med.Chem., 65:14326-14336, 2022 Cited by PubMed Abstract: Bruton's tyrosine kinase (BTK) is a Tec family kinase that plays an essential role in B-cell receptor (BCR) signaling as well as Fcγ receptor signaling in leukocytes. Pharmacological inhibition of BTK has been shown to be effective in treating hematological malignancies and is hypothesized to provide an effective strategy for the treatment of autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. We report the discovery and preclinical properties of JNJ-64264681 (), a covalent, irreversible BTK inhibitor with potent whole blood activity and exceptional kinome selectivity. JNJ-64264681 demonstrated excellent oral efficacy in both cancer and autoimmune models with sustained in vivo target coverage amenable to once daily dosing and has advanced into human clinical studies to investigate safety and pharmacokinetics. PubMed: 36314537DOI: 10.1021/acs.jmedchem.2c01026 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.904 Å) |
Structure validation
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