6MWE
CRYSTAL STRUCTURE OF TIE2 IN COMPLEX WITH DECIPERA COMPOUND DP1919
Summary for 6MWE
| Entry DOI | 10.2210/pdb6mwe/pdb |
| Descriptor | 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) |
| Functional Keywords | tie2, dp1919, emeraldbio, deciphera, transferase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 73998.08 |
| Authors | Chun, L.,Abendroth, J.,Edwards, T.E. (deposition date: 2018-10-29, release date: 2018-11-21, Last modification date: 2023-10-11) |
| Primary citation | 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 Cited by 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: 28838996DOI: 10.1158/1535-7163.MCT-17-0241 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.05 Å) |
Structure validation
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