9TP9
Crystal structure of integrin-linked kinase (ILK) in complex with Alpha-Parvin and dihydroPelitinib
This is a non-PDB format compatible entry.
Summary for 9TP9
| Entry DOI | 10.2210/pdb9tp9/pdb |
| Descriptor | Scaffold protein ILK, Alpha-parvin, ~{N}-[4-[(3-chloranyl-4-fluoranyl-phenyl)amino]-3-cyano-7-ethoxy-quinolin-6-yl]-4-(dimethylamino)butanamide, ... (6 entities in total) |
| Functional Keywords | pseudokinase, focal adhesion, ligand complex, kinase, drug target, cell adhesion |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 46514.34 |
| Authors | |
| Primary citation | Greco, F.A.,Abdul Azeez, K.R.,Mitrovic, M.,Sivashanmugam, S.A.,Schwalm, M.P.,Preuss, F.,Chatterjee, D.,Morasch, V.,Mathea, S.,Hanke, T.,Muller, S.,Knapp, S. Identification and Validation of 3-Cyano-Quinoline Ligands Targeting Integrin-Linked Kinase (ILK). J.Med.Chem., 2026 Cited by PubMed Abstract: Integrin-linked kinase (ILK) is a pseudokinase that directly interacts with β-integrins and plays a pivotal role in regulating focal adhesion function. ILK has been implicated in the development of various diseases, particularly cancer. However, currently, no validated ligands for ILK have been reported. Here, we describe the identification of 3-cyano-quinolines that potently bind to ILK (K = ∼250 nM), and crystallographic studies revealed a type I binding mode. A medicinal chemistry campaign exploring structure-activity relationships (SAR) using a robust parallel synthesis approach provided comprehensive SAR and identified regions amenable to modification. In addition, we demonstrated that the optimized 3-cyano-quinoline (DHP) modulates actin cytoskeletal dynamics. This work highlights the first validated ILK ligands and establishes a foundation for future translational efforts, such as the development of selective PROTACs targeting ILK for degradation by the ubiquitin system. PubMed: 42185966DOI: 10.1021/acs.jmedchem.5c03773 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.45 Å) |
Structure validation
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