3IPY

X-Ray structure of Human Deoxycytidine Kinase in complex with an inhibitor

Summary for 3IPY

• Entry DOI: 10.2210/pdb3ipy/pdb
• Related: 3IPX
• Descriptor: Deoxycytidine kinase, D-MALATE, 4-(1-benzothiophen-2-yl)-6-[4-(2-oxo-2-pyrrolidin-1-ylethyl)piperazin-1-yl]pyrimidine, ... (4 entities in total)
• Functional Keywords: human deoxycytidine kinase, atp-binding, kinase, nucleotide-binding, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens
• Cellular location: Nucleus: P27707
• Total number of polymer chains: 2
• Total formula weight: 59153.03

Authors

Tari, L.W.,Swanson, R.V.,Hunter, M.,Hoffman, I.,Stouch, T.R.,Carson, K.G. (deposition date: 2009-08-18, release date: 2010-08-18, Last modification date: 2023-09-06)

Primary citation

Jessop, T.C.,Tarver, J.E.,Carlsen, M.,Xu, A.,Healy, J.P.,Heim-Riether, A.,Fu, Q.,Taylor, J.A.,Augeri, D.J.,Shen, M.,Stouch, T.R.,Swanson, R.V.,Tari, L.W.,Hunter, M.,Hoffman, I.,Keyes, P.E.,Yu, X.C.,Miranda, M.,Liu, Q.,Swaffield, J.C.,David Kimball, S.,Nouraldeen, A.,Wilson, A.G.,Foushee, A.M.,Jhaver, K.,Finch, R.,Anderson, S.,Oravecz, T.,Carson, K.G.
Lead optimization and structure-based design of potent and bioavailable deoxycytidine kinase inhibitors.
Bioorg.Med.Chem.Lett., 19:6784-6787, 2009

PubMed Abstract: A series of deoxycytidine kinase inhibitors was simultaneously optimized for potency and PK properties. A co-crystal structure then allowed merging this series with a high throughput screening hit to afford a highly potent, selective and orally bioavailable inhibitor, compound 10. This compound showed dose dependent inhibition of deoxycytidine kinase in vivo.

PubMed: 19836232
DOI: 10.1016/j.bmcl.2009.09.081

Experimental method

X-RAY DIFFRACTION (2.54 Å)