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PDBsum entry 3kab
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References listed in PDB file
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Key reference
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Title
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Structure-Guided design of alpha-Amino acid-Derived pin1 inhibitors.
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Authors
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A.J.Potter,
S.Ray,
L.Gueritz,
C.L.Nunns,
C.J.Bryant,
S.F.Scrace,
N.Matassova,
L.Baker,
P.Dokurno,
D.A.Robinson,
A.E.Surgenor,
B.Davis,
J.B.Murray,
C.M.Richardson,
J.D.Moore.
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Ref.
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Bioorg Med Chem Lett, 2010,
20,
586-590.
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PubMed id
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Abstract
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The peptidyl prolyl cis/trans isomerase Pin1 is a promising molecular target for
anti-cancer therapeutics. Here we report the structure-guided evolution of an
indole 2-carboxylic acid fragment hit into a series of
alpha-benzimidazolyl-substituted amino acids. Examples inhibited Pin1 activity
with IC(50) <100nM, but were inactive on cells. Replacement of the
benzimidazole ring with a naphthyl group resulted in a 10-50-fold loss in ligand
potency, but these examples downregulated biomarkers of Pin1 activity and
blocked proliferation of PC3 cells.
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