3LCO

Inhibitor Bound to A DFG-Out structure of the Kinase Domain of CSF-1R

Summary for 3LCO

• Entry DOI: 10.2210/pdb3lco/pdb
• Related: 3LCD
• Descriptor: Macrophage colony-stimulating factor 1 receptor, 3-({4-methoxy-5-[(4-methoxybenzyl)oxy]pyridin-2-yl}methoxy)-5-(1-methyl-1H-pyrazol-4-yl)pyrazin-2-amine (2 entities in total)
• Functional Keywords: atp-binding, disulfide bond, glycoprotein, immunoglobulin domain, kinase, membrane, nucleotide-binding, phosphoprotein, proto-oncogene, receptor, transferase, transmembrane, tyrosine-protein kinase
• Biological source: Homo sapiens (human); More
• Cellular location: Cell membrane; Single-pass type I membrane protein: P07333
• Total number of polymer chains: 1
• Total formula weight: 36729.04

Authors

Kamtekar, S.,Day, J.E.,Reitz, B.A.,Mathis, K.J.,Meyers, M.J. (deposition date: 2010-01-11, release date: 2010-09-15, Last modification date: 2024-02-21)

Primary citation

Meyers, M.J.,Pelc, M.,Kamtekar, S.,Day, J.,Poda, G.I.,Hall, M.K.,Michener, M.L.,Reitz, B.A.,Mathis, K.J.,Pierce, B.S.,Parikh, M.D.,Mischke, D.A.,Long, S.A.,Parlow, J.J.,Anderson, D.R.,Thorarensen, A.
Structure-based drug design enables conversion of a DFG-in binding CSF-1R kinase inhibitor to a DFG-out binding mode.
Bioorg.Med.Chem.Lett., 20:1543-1547, 2010

PubMed Abstract: The work described herein demonstrates the utility of structure-based drug design (SBDD) in shifting the binding mode of an HTS hit from a DFG-in to a DFG-out binding mode resulting in a class of novel potent CSF-1R kinase inhibitors suitable for lead development.

PubMed: 20137931
DOI: 10.1016/j.bmcl.2010.01.078

Experimental method

X-RAY DIFFRACTION (3.4 Å)