6MWE

CRYSTAL STRUCTURE OF TIE2 IN COMPLEX WITH DECIPERA COMPOUND DP1919

6MWE の概要

• エントリーDOI: 10.2210/pdb6mwe/pdb
• 分子名称: Angiopoietin-1 receptor, SULFATE ION, 4-[4-({[3-tert-butyl-1-(quinolin-6-yl)-1H-pyrazol-5-yl]carbamoyl}amino)-3-fluorophenoxy]-N-methylpyridine-2-carboxamide, ... (4 entities in total)
• 機能のキーワード: tie2, dp1919, emeraldbio, deciphera, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 73998.08

構造登録者

Chun, L.,Abendroth, J.,Edwards, T.E. (登録日: 2018-10-29, 公開日: 2018-11-21, 最終更新日: 2023-10-11)

主引用文献

Harney, A.S.,Karagiannis, G.S.,Pignatelli, J.,Smith, B.D.,Kadioglu, E.,Wise, S.C.,Hood, M.M.,Kaufman, M.D.,Leary, C.B.,Lu, W.P.,Al-Ani, G.,Chen, X.,Entenberg, D.,Oktay, M.H.,Wang, Y.,Chun, L.,De Palma, M.,Jones, J.G.,Flynn, D.L.,Condeelis, J.S.
The Selective Tie2 Inhibitor Rebastinib Blocks Recruitment and Function of Tie2
Mol. Cancer Ther., 16:2486-2501, 2017

PubMed Abstract: Tumor-infiltrating myeloid cells promote tumor progression by mediating angiogenesis, tumor cell intravasation, and metastasis, which can offset the effects of chemotherapy, radiation, and antiangiogenic therapy. Here, we show that the kinase switch control inhibitor rebastinib inhibits Tie2, a tyrosine kinase receptor expressed on endothelial cells and protumoral Tie2-expressing macrophages in mouse models of metastatic cancer. Rebastinib reduces tumor growth and metastasis in an orthotopic mouse model of metastatic mammary carcinoma through reduction of Tie2 myeloid cell infiltration, antiangiogenic effects, and blockade of tumor cell intravasation mediated by perivascular Tie2/Vegf-A macrophages in the tumor microenvironment of metastasis (TMEM). The antitumor effects of rebastinib enhance the efficacy of microtubule inhibiting chemotherapeutic agents, either eribulin or paclitaxel, by reducing tumor volume, metastasis, and improving overall survival. Rebastinib inhibition of angiopoietin/Tie2 signaling impairs multiple pathways in tumor progression mediated by protumoral Tie2 macrophages, including TMEM-dependent dissemination and angiopoietin/Tie2-dependent angiogenesis. Rebastinib is a promising therapy for achieving Tie2 inhibition in cancer patients. .

PubMed: 28838996
DOI: 10.1158/1535-7163.MCT-17-0241

実験手法

X-RAY DIFFRACTION (2.05 Å)