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Your search keyword '"Bryant CJ"' showing total 2 results
Start Over Author "Bryant CJ" Publisher elsevier science ltd
2 results on '"Bryant CJ"'

1. Discovery of cell-active phenyl-imidazole Pin1 inhibitors by structure-guided fragment evolution.

Author

Potter A, Oldfield V, Nunns C, Fromont C, Ray S, Northfield CJ, Bryant CJ, Scrace SF, Robinson D, Matossova N, Baker L, Dokurno P, Surgenor AE, Davis B, Richardson CM, Murray JB, and Moore JD

Subjects
Caco-2 Cells, Drug Discovery, Humans, Imidazoles chemistry, Models, Molecular, Molecular Structure, NIMA-Interacting Peptidylprolyl Isomerase, Imidazoles pharmacology, Peptidylprolyl Isomerase antagonists & inhibitors
Abstract

Pin1 is an emerging oncology target strongly implicated in Ras and ErbB2-mediated tumourigenesis. Pin1 isomerizes bonds linking phospho-serine/threonine moieties to proline enabling it to play a key role in proline-directed kinase signalling. Here we report a novel series of Pin1 inhibitors based on a phenyl imidazole acid core that contains sub-μM inhibitors. Compounds have been identified that block prostate cancer cell growth under conditions where Pin1 is essential., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Published
2010
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2. Structure-guided design of alpha-amino acid-derived Pin1 inhibitors.

Author

Potter AJ, Ray S, Gueritz L, Nunns CL, Bryant CJ, Scrace SF, Matassova N, Baker L, Dokurno P, Robinson DA, Surgenor AE, Davis B, Murray JB, Richardson CM, and Moore JD

Subjects
Amino Acids chemical synthesis, Amino Acids pharmacology, Antineoplastic Agents chemical synthesis, Antineoplastic Agents pharmacology, Benzimidazoles chemistry, Binding Sites, Cell Line, Tumor, Crystallography, X-Ray, Enzyme Inhibitors chemical synthesis, Enzyme Inhibitors pharmacology, Humans, Hydrogen Bonding, Indoles chemistry, NIMA-Interacting Peptidylprolyl Isomerase, Peptidylprolyl Isomerase metabolism, Structure-Activity Relationship, Amino Acids chemistry, Antineoplastic Agents chemistry, Enzyme Inhibitors chemistry, Peptidylprolyl Isomerase antagonists & inhibitors
Abstract

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., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Published
2010
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