8V5H
Crystal structure of MASTL Kinase domain in complex with an inhibitor
This is a non-PDB format compatible entry.
Summary for 8V5H
| Entry DOI | 10.2210/pdb8v5h/pdb |
| Descriptor | Serine/threonine-protein kinase greatwall, (3M)-N~6~-ethyl-3-(1-methyl-1H-imidazol-5-yl)-2,7-naphthyridine-1,6-diamine (2 entities in total) |
| Functional Keywords | human greatwall, kinase, mastl kinase domain, inhibitor, transferase, transferase-inhibitor complex, transferase/inhibitor |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 1 |
| Total formula weight | 38658.08 |
| Authors | |
| Primary citation | Gallego, R.A.,Scales, S.,Toledo, C.,Auth, M.,Bernier, L.,Berry, M.,Brun, S.,Chung, L.,Davis, C.,Diehl, W.,Dress, K.,Eisele, K.,Elleraas, J.,Ewanicki, J.,Fobian, Y.,Greasley, S.,Greenwald, E.C.,Johnson, T.W.,Khamphavong, P.,Lafontaine, J.,Li, J.,Linton, A.,Maestre, M.,Miller, N.,Murtaza, A.,Patman, R.L.,Quinlan, C.L.,Ramms, D.J.,Richardson, P.,Sach, N.,Salomon-Ferrer, R.,Silva, F.,Timofeevski, S.,Tran, P.,Tran-Dube, M.,Wang, F.,Wang, W.,Wythes, M.,Yang, S.,Zou, A.,VanArsdale, T.,McAlpine, I. Discovery of Highly Selective Inhibitors of Microtubule-Associated Serine/Threonine Kinase-like (MASTL). J.Med.Chem., 67:19234-19246, 2024 Cited by PubMed Abstract: By virtue of its role in cellular proliferation, microtubule-associated serine/threonine kinase-like (MASTL) represents a novel target and a first-in-class (FIC) opportunity to provide a new impactful therapeutic agent to oncology patients. Herein, we describe a hit-to-lead optimization effort that resulted in the delivery of two highly selective MASTL inhibitors. Key strategies leveraged to enable this work included structure-based drug design (SBDD), analysis of lipophilic efficiency (LipE) and novel synthesis. The resulting advanced lead compounds enabled a tumor growth inhibition study which was pivotal in assessing the potential value of MASTL as an oncology therapeutic target. PubMed: 39499084DOI: 10.1021/acs.jmedchem.4c01659 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.74 Å) |
Structure validation
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