3T9T

Crystal structure of BTK mutant (F435T,K596R) complexed with Imidazo[1,5-a]quinoxaline

Summary for 3T9T

• Entry DOI: 10.2210/pdb3t9t/pdb
• Descriptor: Tyrosine-protein kinase ITK/TSK, (2Z)-4-(dimethylamino)-N-{7-fluoro-4-[(2-methylphenyl)amino]imidazo[1,5-a]quinoxalin-8-yl}-N-methylbut-2-enamide, GLYCEROL, ... (4 entities in total)
• Functional Keywords: kinase domain, alpha/beta, atp binding, phosphorylation, intracellular, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: Q08881
• Total number of polymer chains: 1
• Total formula weight: 31075.49

Authors

Han, S.,Caspers, N. (deposition date: 2011-08-03, release date: 2011-10-12, Last modification date: 2024-10-30)

Primary citation

Kim, K.H.,Maderna, A.,Schnute, M.E.,Hegen, M.,Mohan, S.,Miyashiro, J.,Lin, L.,Li, E.,Keegan, S.,Lussier, J.,Wrocklage, C.,Nickerson-Nutter, C.L.,Wittwer, A.J.,Soutter, H.,Caspers, N.,Han, S.,Kurumbail, R.,Dunussi-Joannopoulos, K.,Douhan, J.,Wissner, A.
Imidazo[1,5-a]quinoxalines as irreversible BTK inhibitors for the treatment of rheumatoid arthritis.
Bioorg.Med.Chem.Lett., 21:6258-6263, 2011

PubMed Abstract: Imidazo[1,5-a]quinoxalines were synthesized that function as irreversible Bruton's tyrosine kinase (BTK) inhibitors. The syntheses and SAR of this series of compounds are presented as well as the X-ray crystal structure of the lead compound 36 in complex with a gate-keeper variant of ITK enzyme. The lead compound showed good in vivo efficacy in preclinical RA models.

PubMed: 21958547
DOI: 10.1016/j.bmcl.2011.09.008

Experimental method

X-RAY DIFFRACTION (1.65 Å)