6I10
CRYSTAL STRUCTURE OF FASCIN IN COMPLEX WITH COMPOUND 2
Summary for 6I10
| Entry DOI | 10.2210/pdb6i10/pdb |
| Descriptor | Fascin, 1-[(3~{R})-1,1-bis(oxidanylidene)thiolan-3-yl]-5-[(3,4-dichlorophenyl)methyl]pyrazolo[3,4-d]pyrimidin-4-one, ACETATE ION, ... (5 entities in total) |
| Functional Keywords | actin bundling, small molecule inhibition, structural protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 55260.40 |
| Authors | Schuettelkopf, A.W. (deposition date: 2018-10-27, release date: 2019-02-27, Last modification date: 2024-01-24) |
| Primary citation | Francis, S.,Croft, D.,Schuttelkopf, A.W.,Parry, C.,Pugliese, A.,Cameron, K.,Claydon, S.,Drysdale, M.,Gardner, C.,Gohlke, A.,Goodwin, G.,Gray, C.H.,Konczal, J.,McDonald, L.,Mezna, M.,Pannifer, A.,Paul, N.R.,Machesky, L.,McKinnon, H.,Bower, J. Structure-based design, synthesis and biological evaluation of a novel series of isoquinolone and pyrazolo[4,3-c]pyridine inhibitors of fascin 1 as potential anti-metastatic agents. Bioorg.Med.Chem.Lett., 29:1023-1029, 2019 Cited by PubMed Abstract: Fascin is an actin binding and bundling protein that is not expressed in normal epithelial tissues but overexpressed in a variety of invasive epithelial tumors. It has a critical role in cancer cell metastasis by promoting cell migration and invasion. Here we report the crystal structures of fascin in complex with a series of novel and potent inhibitors. Structure-based elaboration of these compounds enabled the development of a series with nanomolar affinities for fascin, good physicochemical properties and the ability to inhibit fascin-mediated bundling of filamentous actin. These compounds provide promising starting points for fascin-targeted anti-metastatic therapies. PubMed: 30773430DOI: 10.1016/j.bmcl.2019.01.035 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
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