7TNH

Crystal structure of CSF1R kinase domain in complex with DP-6233

7TNH の概要

• エントリーDOI: 10.2210/pdb7tnh/pdb
• 分子名称: Macrophage colony-stimulating factor 1 receptor,Fibroblast growth factor receptor 1 chimera, SODIUM ION, CHLORIDE ION, ... (5 entities in total)
• 機能のキーワード: human csr1r kinase, cancer, 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: 39083.07

構造登録者

Edwards, T.E.,Arakaki, T.L.,Chun, L.,Flynn, D.L. (登録日: 2022-01-21, 公開日: 2022-08-24, 最終更新日: 2023-10-18)

主引用文献

Caldwell, T.M.,Kaufman, M.D.,Wise, S.C.,Mi Ahn, Y.,Hood, M.M.,Lu, W.P.,Patt, W.C.,Samarakoon, T.,Vogeti, L.,Vogeti, S.,Yates, K.M.,Bulfer, S.L.,Le Bourdonnec, B.,Smith, B.D.,Flynn, D.L.
Discovery of acyl ureas as highly selective small molecule CSF1R kinase inhibitors.
Bioorg.Med.Chem.Lett., 74:128929-128929, 2022

PubMed Abstract: Based on the structure of an early lead identified in Deciphera's proprietary compound collection of switch control kinase inhibitors and using a combination of medicinal chemistry guided structure activity relationships and structure-based drug design, a novel series of potent acyl urea-based CSF1R inhibitors was identified displaying high selectivity for CSF1R versus the other members of the Type III receptor tyrosine kinase (RTK) family members (KIT, PDGFR-α, PDGFR-β, and FLT3), VEGFR2 and MET. Based on in vitro biology, in vitro ADME and in vivo PK/PD studies, compound 10 was selected as an advanced lead for Deciphera's CSF1R research program.

PubMed: 35961461
DOI: 10.1016/j.bmcl.2022.128929

実験手法

X-RAY DIFFRACTION (2.7 Å)