Designing of kinase hinge binders: A medicinal chemistry perspective
Vikas Sharma1, Mohit Gupta2,3
1School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, India.
Abstract:
Protein kinases are key regulators of cellular signaling and play a critical role in oncogenesis. Inhibitors of protein kinases are pursued by both industry and academia as a promising target for cancer therapy. Within the protein kinases, the ATP site has produced more than 40 FDA-approved drugs. The ATP site is broadly composed of a hinge region, gatekeeper residues, DFG-loop, ribose pocket, and other hydrophobic regions. The hinge region in the ATP site can be used for designing potent inhibitors. In this review, we discuss some representative studies that will highlight the interactions of heterocyclic compounds with hinge regions of different kinases like BRAF kinase, EGRF kinase, MAP kinase, and Mps1 kinase.
Related Concept Videos
Ligand Binding and Linkage
The Equilibrium Binding Constant and Binding Strength
Ligand Binding Sites
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Transducer Mechanism: Enzyme-Linked Receptors
Major types that are helpful drug targets include:
Induced-fit Model
Enzymes exhibit substrate specificity, meaning that they can only bind to certain substrates. This is mainly determined by the shape and chemical...
Protein-protein Interfaces


