Publications by authors named "E Freyne"
Fibroblast growth factor (FGF) signaling plays critical roles in key biological processes ranging from embryogenesis to wound healing and has strong links to several hallmarks of cancer. Genetic alterations in FGF receptor () family members are associated with increased tumor growth, metastasis, angiogenesis, and decreased survival. JNJ-42756493, erdafitinib, is an orally active small molecule with potent tyrosine kinase inhibitory activity against all four FGFR family members and selectivity versus other highly related kinases.
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- 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 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 Synopsis
- Researchers identified and characterized two new inhibitors specifically targeting the fibroblast growth factor receptor (FGFR) family, which are important for cell signaling in various cancers.
- These inhibitors show a strong preference for FGFR over a similar receptor, VEGFR2, when tested in lab cell lines and living organisms.
- The effectiveness of these inhibitors was evaluated across different human tumor cell lines with known genetic changes that activate FGFR, suggesting their potential clinical use in treating FGFR-related diseases.
Pursuing our efforts in designing 5-pyrimidylhydroxamic acid anti-cancer agents, we have identified a new series of potent histone deacetylase (HDAC) inhibitors. These compounds exhibit enzymatic HDAC inhibiting properties with IC(50) values in the nanomolar range and inhibit tumor cell proliferation at similar levels. Good solubility, moderate bioavailability, and promising in vivo activity in xenograft model made this series of compounds interesting starting points to design new potent HDAC inhibitors.
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