8W1L

Structure of CSF1R kinase domain in complex with Cpd 32

これはPDB形式変換不可エントリーです。

8W1L の概要

• エントリーDOI: 10.2210/pdb8w1l/pdb
• 分子名称: 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)
• 機能のキーワード: inhibitor complex, transferase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 38636.01

構造登録者

Kothe, M.,Chodaparambil, J. (登録日: 2024-02-16, 公開日: 2024-05-29)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.26 Å)