AI Article Synopsis
- A new Type II kinase inhibitor has been developed specifically for maternal embryonic leucine zipper kinase (MELK) using a method known as structure-based ligand design.
- This approach involved detailed structural analysis of the protein-ligand interactions through techniques like X-ray crystallography, which helped identify a unique pocket for the inhibitor to bind.
- The optimized inhibitor is highly effective, operating at low nanomolar concentrations and able to easily enter cells, making it a promising tool for researching MELK's biological functions.
Article Abstract
A novel Type II kinase inhibitor chemotype has been identified for maternal embryonic leucine zipper kinase (MELK) using structure-based ligand design. The strategy involved structural characterization of an induced DFG-out pocket by protein-ligand X-ray crystallography and incorporation of a slender linkage capable of bypassing a large gate-keeper residue, thus enabling design of molecules accessing both hinge and induced pocket regions. Optimization of an initial hit led to the identification of a low-nanomolar, cell-penetrant Type II inhibitor suitable for use as a chemical probe for MELK.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4291807 | PMC |
| http://dx.doi.org/10.1021/ml5001273 | DOI Listing |
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