8W1L

Structure of CSF1R kinase domain in complex with Cpd 32

This is a non-PDB format compatible entry.

Summary for 8W1L

• Entry DOI: 10.2210/pdb8w1l/pdb
• Descriptor: Macrophage colony-stimulating factor 1 receptor,CSF1R, [3-({3-methoxy-4-[(6-methoxypyridin-3-yl)methoxy]phenyl}methyl)-3H-imidazo[4,5-b]pyridin-6-yl](2-oxa-6-azaspiro[3.3]heptan-6-yl)methanone, GLYCEROL, ... (5 entities in total)
• Functional Keywords: inhibitor complex, transferase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 1
• Total formula weight: 38636.01

Authors

Kothe, M.,Chodaparambil, J. (deposition date: 2024-02-16, release date: 2024-05-29)

Primary citation

Kane Jr., J.L.,Asmussen, G.,Batchelor, J.,Cromwell, M.,Fezoui, M.,Fitzgerald, M.,Giese, B.,Gladysheva, T.,Holley, S.,Keefe, K.,Kothe, M.,Lam, B.,Lim, S.,Liu, J.,Ma, L.,Metz, M.,Scholte, A.A.,Shum, P.,Wei, L.,Woodworth, L.,Edling, A.
Identification of Selective Imidazopyridine CSF1R Inhibitors.
Acs Med.Chem.Lett., 15:722-730, 2024

PubMed Abstract: Colony stimulating factor-1 receptor (CSF1R or c-FMS), a class III receptor tyrosine kinase expressed on members of the mononuclear phagocyte system (MPS), plays a key role in the proper functioning of macrophages, microglia, and related cells. Aberrant signaling through CSF1R has been associated with a variety of disease states, including cancer, inflammation, and neurodegeneration. In this Letter, we detail our efforts to develop novel CSF1R inhibitors. Drawing on previously described compounds, including GW2580 (), we have discovered a novel series of compounds based on the imidazo[4,5-]pyridine scaffold. Initial structure-activity relationship studies culminated in the identification of , a lead compound with potent CSF1R biochemical and cellular activity, acceptable ADME properties, and oral exposure in rat.

PubMed: 38746878
DOI: 10.1021/acsmedchemlett.4c00110

Experimental method

X-RAY DIFFRACTION (2.26 Å)