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PDBsum entry 4qml
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Transferase/transferase inhibitor
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PDB id
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4qml
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References listed in PDB file
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Key reference
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Title
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Discovery of diverse small-Molecule inhibitors of mammalian sterile20-Like kinase 3 (mst3).
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Authors
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S.H.Olesen,
J.Y.Zhu,
M.P.Martin,
E.Schönbrunn.
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Ref.
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Chemmedchem, 2016,
11,
1137-1144.
[DOI no: ]
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PubMed id
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Abstract
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Increasing evidence suggests key roles for members of the mammalian
Sterile20-like (MST) family of kinases in many aspects of biology. MST3 is a
member of the STRIPAK complex, the deregulation of which has recently been
associated with cancer cell migration and metastasis. Targeting MST3 with
small-molecule inhibitors may be beneficial for the treatment of certain
cancers, but little information exists on the potential of kinase inhibitor
scaffolds to engage with MST3. In this study we screened MST3 against a library
of 277 kinase inhibitors using differential scanning fluorimetry and confirmed
14 previously unknown MST3 inhibitors by X-ray crystallography. These compounds,
of which eight are in clinical trials or FDA approved, comprise nine distinct
chemical scaffolds that inhibit MST3 enzymatic activity with IC50 values between
0.003 and 23 μm. The structure-activity relationships explain the
differential inhibitory activity of these compounds against MST3 and the
structural basis for high binding potential, the information of which may serve
as a framework for the rational design of MST3-selective inhibitors as potential
therapeutics and to interrogate the function of this enzyme in diseased cells.
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