Abstract
Fmoc-pSer-Psi[(Z)CHC]-Pro-(2)-N-(3)-ethylaminoindole 1, showed moderate inhibition towards the mitotic regulator, Pin1 (IC(50)=28.3microM). To improve the cell permeability, the charged phosphate was masked as the bis-pivaloyloxymethyl (POM) phosphate in Fmoc-(bisPOM)-pSer-Psi[(Z)CHC]-Pro-(2)-N-(3)-ethylaminoindole 2. Antiproliferative activity towards A2780 ovarian cancer cells of 1 (IC(50)=46.2microM) was improved significantly in 2 (IC(50)=26.9microM), comparable to the IC(50) of 1 towards Pin1 enzymatic activity.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
MeSH terms
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / metabolism
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Antineoplastic Agents / pharmacology
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Cell Line, Tumor
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / metabolism
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Enzyme Inhibitors / pharmacology
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Growth Inhibitors / chemistry
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Growth Inhibitors / metabolism
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Growth Inhibitors / pharmacology
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Humans
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NIMA-Interacting Peptidylprolyl Isomerase
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Peptidylprolyl Isomerase / antagonists & inhibitors*
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Peptidylprolyl Isomerase / metabolism
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Phosphorylation
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Prodrugs / chemistry*
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Prodrugs / metabolism
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Prodrugs / pharmacology*
Substances
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Antineoplastic Agents
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Enzyme Inhibitors
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Growth Inhibitors
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NIMA-Interacting Peptidylprolyl Isomerase
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Prodrugs
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PIN1 protein, human
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Peptidylprolyl Isomerase