5T68

Crystal structure of Syk catalytic domain in complex with a furo[3,2-d]pyrimidine

Summary for 5T68

• Entry DOI: 10.2210/pdb5t68/pdb
• Descriptor: Tyrosine-protein kinase SYK, N~4~-cyclopropyl-N~2~-(3-methyl-1H-indazol-6-yl)furo[3,2-d]pyrimidine-2,4-diamine (3 entities in total)
• Functional Keywords: spleen tyrosine kinase syk catalytic domain, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (Human)
• Cellular location: Cell membrane : P43405
• Total number of polymer chains: 2
• Total formula weight: 68408.71

Authors

Argiriadi, M.A.,Hoemann, M.,Wilson, N.,Banach, D.,Burchat, A.,Calderwood, D.,Clapham, B.,Cox, P.,Duignan, D.B.,Konopacki, D.,Somal, G.,Vasudevan, A. (deposition date: 2016-09-01, release date: 2016-10-26, Last modification date: 2023-10-04)

Primary citation

Hoemann, M.,Wilson, N.,Argiriadi, M.,Banach, D.,Burchat, A.,Calderwood, D.,Clapham, B.,Cox, P.,Duignan, D.B.,Konopacki, D.,Somal, G.,Vasudevan, A.
Synthesis and optimization of furano[3,2-d]pyrimidines as selective spleen tyrosine kinase (Syk) inhibitors.
Bioorg. Med. Chem. Lett., 26:5562-5567, 2016

PubMed Abstract: A series of furano[3,2-d]pyrimidine Syk inhibitors were synthesized and optimized for their enzyme potency and selectivity versus other kinases. In addition, ADME properties were assessed and compounds were prepared with optimized profiles for in vivo experiments. Compound 23 was identified as having acceptable pharmacokinetic properties and demonstrated efficacy in a rat collagen induced arthritis model.

PubMed: 27789138
DOI: 10.1016/j.bmcl.2016.09.077

Experimental method

X-RAY DIFFRACTION (2.93 Å)