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PDBsum entry 4g9r
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Transferase/transferase inhibitor
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PDB id
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4g9r
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References listed in PDB file
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Key reference
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Title
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Pyrazolopyridine inhibitors of b-Raf(V600e). Part 4: rational design and kinase selectivity profile of cell potent type ii inhibitors.
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Authors
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S.Wenglowsky,
D.Moreno,
E.R.Laird,
S.L.Gloor,
L.Ren,
T.Risom,
J.Rudolph,
H.L.Sturgis,
W.C.Voegtli.
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Ref.
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Bioorg Med Chem Lett, 2012,
22,
6237-6241.
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PubMed id
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Abstract
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Cell potent inhibitors of B-Raf(V600E) that bind to the kinase in the DFG-out
conformation are reported. These compounds utilize the hinge-binding group and
lipophilic linker from a previously disclosed series of B-Raf(V600E) inhibitors
that bind to the kinase in an atypical DFG-in, αC-helix-out conformation. This
new series demonstrates that DFG-out kinase inhibitors can be rationally
designed from related inhibitors which utilize an unconventional binding mode.
Kinase selectivity profiles are compared. The pattern of kinase selectivity was
found to be determined by the feature of the inhibitor which extends into the
back pocket of the kinase and leads to the kinase conformation, rather than by
the hinge-binding group or other minor modifications.
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