6GIN
Crystal structure of the ACVR1 (ALK2) kinase in complex with an Quinazolinone based ALK2 inhibitor with a 4-morpholinophenyl solvent accessible group.
Summary for 6GIN
| Entry DOI | 10.2210/pdb6gin/pdb |
| Descriptor | Activin receptor type-1, 3-(4-morpholin-4-ylphenyl)-6-quinolin-4-yl-quinazolin-4-one, SULFATE ION, ... (5 entities in total) |
| Functional Keywords | kinase, bmp, inhibitor, signalling, signaling protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 70768.89 |
| Authors | Williams, E.,Hudson, L.,Bezerra, G.A.,Kopec, J.,Mahajan, P.,Kupinska, K.,Hoelder, S.,Burgess-Brown, N.,von Delft, F.,Arrowsmith, C.H.,Edwards, A.M.,Bountra, C.,Bullock, A.N. (deposition date: 2018-05-14, release date: 2018-05-23, Last modification date: 2024-01-17) |
| Primary citation | Hudson, L.,Mui, J.,Vazquez, S.,Carvalho, D.M.,Williams, E.,Jones, C.,Bullock, A.N.,Hoelder, S. Novel Quinazolinone Inhibitors of ALK2 Flip between Alternate Binding Modes: Structure-Activity Relationship, Structural Characterization, Kinase Profiling, and Cellular Proof of Concept. J. Med. Chem., 61:7261-7272, 2018 Cited by PubMed Abstract: Structure-activity relationship and crystallographic data revealed that quinazolinone-containing fragments flip between two distinct modes of binding to activin receptor-like kinase-2 (ALK2). We explored both binding modes to discover potent inhibitors and characterized the chemical modifications that triggered the flip in binding mode. We report kinase selectivity and demonstrate that compounds of this series modulate ALK2 in cancer cells. These inhibitors are attractive starting points for the discovery of more advanced ALK2 inhibitors. PubMed: 30085668DOI: 10.1021/acs.jmedchem.8b00782 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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