5ZAN
Crystal Structure of Aurora-A in complex with a new Quinazoline inhibitor
Summary for 5ZAN
| Entry DOI | 10.2210/pdb5zan/pdb |
| Descriptor | Aurora kinase A, 7-(4-methylpiperazin-1-yl)-N-(5-methyl-1H-pyrazol-3-yl)-2-[(E)-2-phenylethenyl]quinazolin-4-amine (2 entities in total) |
| Functional Keywords | drug design, transferase, transferase-inhibitor complex, transferase/inhibitor |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 32985.88 |
| Authors | |
| Primary citation | Long, L.,Zhang, B.,Peng, W.,Pan, Y.,Zhai, H.,Cheng, B.,Tu, Z.,Long, Z.,Zhou, H.,Liu, Q.,Lu, G. Optimization of Novel Quinazolines as Potent Aurora Kinase Inhibitors for Triple-Negative Breast Cancer Treatment. J.Med.Chem., 68:18197-18215, 2025 Cited by PubMed Abstract: This work describes the discovery of a new series of Aurora kinase inhibitors based on quinazoline skeleton derived from , as well as the first X-ray cocrystal structure complexes of vinyl-quinazoline with Aurora A. Replacing pyrimidine with quinazoline improved anticancer activity and facilitated cocrystal formation. Compounds and showed excellent Aurora A kinase inhibition, with IC values of 6.0 and 2.8 nM, respectively. demonstrated superior activity against TNBC MDA-MB-231 cells with an IC value of 48 nM and achieved 59% tumor growth inhibition in xenograft models, vs 's 33% with no observable toxicity. Mechanistic studies using immunoblotting, immunofluorescence staining, and flow cytometry showed that outperforms in inhibiting Aurora A kinase activation, preventing spindle formation, arresting the cell cycle, and inducing cell apoptosis. Thus, has the potential for further optimization and is a promising anticancer drug candidate. PubMed: 40852972DOI: 10.1021/acs.jmedchem.5c00107 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.85 Å) |
Structure validation
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