AI Article Synopsis
- Fragment-based drug design was used effectively to target maternal embryonic leucine zipper kinase (MELK).
- Researchers identified an initial low-affinity fragment that bound to MELK's hinge region in a unique way.
- This fragment was then optimized into a potent, cell-penetrating inhibitor with low nanomolar affinity, making it a valuable tool for studying MELK's biological roles.
Article Abstract
Fragment-based drug design was successfully applied to maternal embryonic leucine zipper kinase (MELK). A low affinity (160 μM) fragment hit was identified, which bound to the hinge region with an atypical binding mode, and this was optimized using structure-based design into a low-nanomolar and cell-penetrant inhibitor, with a good selectivity profile, suitable for use as a chemical probe for elucidation of MELK biology.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4291735 | PMC |
| http://dx.doi.org/10.1021/ml5001245 | DOI Listing |
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