Colony stimulating factor-1 receptor as a target for small molecule inhibitors.

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Mashkani B, Griffith R, Ashman LK

Colony stimulating factor-1 receptor as a target for small molecule inhibitors.

Bioorg Med Chem. 2010 Mar 1;18(5):1789-97. doi: 10.1016/j.bmc.2010.01.056. Epub 2010 Jan 28.

PubMed ID

20156689 [ View in PubMed

]

Abstract

Imatinib, dasatinib, sunitinib, CEP-701, and PKC-412, ATP-competitive small molecule inhibitors of type III receptor tyrosine kinases c-KIT and/or FLT3, were evaluated for binding to the closely related receptor, FMS, by docking into models of inactive and active conformations of the FMS kinase domain. To confirm the docking predictions, the drugs were tested for their activity and selectivity in inhibiting cell proliferation and FMS phosphorylation upon stimulation by the FMS ligand, CSF-1. All five drugs inhibited FMS activity. Imatinib, dasatinib and CEP-701 represent three different types of interactions determining drug potency and selectivity.

DrugBank Data that Cites this Article

Polypeptides

Name	UniProt ID
Macrophage colony-stimulating factor 1 receptor	P07333	Details

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Imatinib	Macrophage colony-stimulating factor 1 receptor	IC 50 (nM)	1274	N/A	N/A	Details
Sunitinib	Macrophage colony-stimulating factor 1 receptor	IC 50 (nM)	155	N/A	N/A	Details