5EDQ

EGFR kinase (T790M/L858R) with inhibitor compound 15: ~{N}-(7-chloranyl-1~{H}-indazol-3-yl)-7,7-dimethyl-2-(1~{H}-pyrazol-4-yl)-5~{H}-furo[3,4-d]pyrimidin-4-amine

5EDQ の概要

• エントリーDOI: 10.2210/pdb5edq/pdb
• 関連するPDBエントリー: 5EDP 5EDR
• 分子名称: Epidermal growth factor receptor, ~{N}-(7-chloranyl-1~{H}-indazol-3-yl)-7,7-dimethyl-2-(1~{H}-pyrazol-4-yl)-5~{H}-furo[3,4-d]pyrimidin-4-amine (2 entities in total)
• 機能のキーワード: protein kinase, inhibitor, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cell membrane; Single-pass type I membrane protein. Isoform 2: Secreted: P00533
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 37931.22

構造登録者

Eigenbrot, C.,Yu, C. (登録日: 2015-10-21, 公開日: 2015-12-02, 最終更新日: 2024-03-06)

主引用文献

Hanan, E.J.,Baumgardner, M.,Bryan, M.C.,Chen, Y.,Eigenbrot, C.,Fan, P.,Gu, X.H.,La, H.,Malek, S.,Purkey, H.E.,Schaefer, G.,Schmidt, S.,Sideris, S.,Yen, I.,Yu, C.,Heffron, T.P.
4-Aminoindazolyl-dihydrofuro[3,4-d]pyrimidines as non-covalent inhibitors of mutant epidermal growth factor receptor tyrosine kinase.
Bioorg.Med.Chem.Lett., 26:534-539, 2016

PubMed Abstract: The treatment of epidermal growth factor receptor (EGFR)-driven non-small cell lung cancers with the T790M resistance mutation remains a significant unmet medical need. We report the identification of 4-aminoindazolyl-dihydrofuro[3,4-d]pyrimidines as non-covalent inhibitors of EGFR, with excellent activity against the T790M resistance double mutants and initial single activating mutants. Using an optimization strategy focused on structure-based design and improving PK properties through metabolite identification, we obtained advanced leads with high oral exposure.

PubMed: 26639762
DOI: 10.1016/j.bmcl.2015.11.078

実験手法

X-RAY DIFFRACTION (2.8 Å)