3V5Q

Discovery of a selective TRK Inhibitor with efficacy in rodent cancer tumor models

3V5Q の概要

• エントリーDOI: 10.2210/pdb3v5q/pdb
• 分子名称: NT-3 growth factor receptor, CHLORIDE ION, 1-(3-{[(3Z)-2-oxo-3-(1H-pyrrol-2-ylmethylidene)-2,3-dihydro-1H-indol-6-yl]amino}phenyl)-3-[3-(trifluoromethyl)phenyl]urea, ... (4 entities in total)
• 機能のキーワード: kinase domain, kinase, phosphorylation, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Membrane; Single-pass type I membrane protein: Q16288
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 68923.39

構造登録者

Kreusch, A. (登録日: 2011-12-16, 公開日: 2012-02-08, 最終更新日: 2024-02-28)

主引用文献

Albaugh, P.,Fan, Y.,Mi, Y.,Sun, F.,Adrian, F.,Li, N.,Jia, Y.,Sarkisova, Y.,Kreusch, A.,Hood, T.,Lu, M.,Liu, G.,Huang, S.,Liu, Z.,Loren, J.,Tuntland, T.,Karanewsky, D.S.,Seidel, H.M.,Molteni, V.
Discovery of GNF-5837, a Selective TRK Inhibitor with Efficacy in Rodent Cancer Tumor Models.
ACS Med Chem Lett, 3:140-145, 2012

PubMed Abstract: Neurotrophins and their receptors (TRKs) play key roles in the development of the nervous system and the maintenance of the neural network. Accumulating evidence points to their role in malignant transformations, chemotaxis, metastasis, and survival signaling and may contribute to the pathogenesis of a variety of tumors of both neural and non-neural origin. By screening the GNF kinase collection, a series of novel oxindole inhibitors of TRKs were identified. Optimization led to the identification of GNF-5837 (22), a potent, selective, and orally bioavailable pan-TRK inhibitor that inhibited tumor growth in a mouse xenograft model derived from RIE cells expressing both TRKA and NGF. The properties of 22 make it a good tool for the elucidation of TRK biology in cancer and other nononcology indications.

PubMed: 24900443
DOI: 10.1021/ml200261d

実験手法

X-RAY DIFFRACTION (2.2001 Å)