Three classes of glucocerebrosidase inhibitors identified by quantitative high-throughput screening are chaperone leads for Gaucher disease.

PubWeight™: 1.70‹?› | Rank: Top 3%

🔗 View Article (PMC 1936979)

Published in Proc Natl Acad Sci U S A on August 01, 2007

Authors

Wei Zheng1, Janak Padia, Daniel J Urban, Ajit Jadhav, Ozlem Goker-Alpan, Anton Simeonov, Ehud Goldin, Douglas Auld, Mary E LaMarca, James Inglese, Christopher P Austin, Ellen Sidransky

Author Affiliations

1: NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, 9800 Medical Center Drive, MSC 3370, Bethesda, MD 20892-3370, USA.

Articles citing this

Compound Management for Quantitative High-Throughput Screening. JALA Charlottesv Va (2008) 2.11

A robotic platform for quantitative high-throughput screening. Assay Drug Dev Technol (2008) 1.90

Treating lysosomal storage diseases with pharmacological chaperones: from concept to clinics. EMBO Mol Med (2009) 1.49

Quantitative analyses of aggregation, autofluorescence, and reactivity artifacts in a screen for inhibitors of a thiol protease. J Med Chem (2010) 1.45

Partial restoration of mutant enzyme homeostasis in three distinct lysosomal storage disease cell lines by altering calcium homeostasis. PLoS Biol (2008) 1.42

Identification and characterization of ambroxol as an enzyme enhancement agent for Gaucher disease. J Biol Chem (2009) 1.39

Effects of pH and iminosugar pharmacological chaperones on lysosomal glycosidase structure and stability. Biochemistry (2009) 1.38

Comprehensive characterization of cytochrome P450 isozyme selectivity across chemical libraries. Nat Biotechnol (2009) 1.30

Lysosomal storage disorders in the newborn. Pediatrics (2009) 1.29

Identification and characterization of pharmacological chaperones to correct enzyme deficiencies in lysosomal storage disorders. Assay Drug Dev Technol (2011) 1.28

Developing inhibitors of glycan processing enzymes as tools for enabling glycobiology. Nat Chem Biol (2012) 1.21

A generalizable pre-clinical research approach for orphan disease therapy. Orphanet J Rare Dis (2012) 1.16

Induced pluripotent stem cell model recapitulates pathologic hallmarks of Gaucher disease. Proc Natl Acad Sci U S A (2012) 1.15

Discovery, structure-activity relationship, and biological evaluation of noninhibitory small molecule chaperones of glucocerebrosidase. J Med Chem (2012) 1.14

Macrophage models of Gaucher disease for evaluating disease pathogenesis and candidate drugs. Sci Transl Med (2014) 1.11

Identification of pharmacological chaperones for Gaucher disease and characterization of their effects on beta-glucocerebrosidase by hydrogen/deuterium exchange mass spectrometry. Chembiochem (2008) 1.10

High throughput screening for small molecule therapy for Gaucher disease using patient tissue as the source of mutant glucocerebrosidase. PLoS One (2012) 1.07

Evaluation of quinazoline analogues as glucocerebrosidase inhibitors with chaperone activity. J Med Chem (2011) 1.05

Pharmacological Chaperone Therapy: Preclinical Development, Clinical Translation, and Prospects for the Treatment of Lysosomal Storage Disorders. Mol Ther (2015) 1.04

Ambroxol as a pharmacological chaperone for mutant glucocerebrosidase. Blood Cells Mol Dis (2012) 1.02

Optimization and validation of two miniaturized glucocerebrosidase enzyme assays for high throughput screening. Comb Chem High Throughput Screen (2008) 0.99

The pilot phase of the NIH Chemical Genomics Center. Curr Top Med Chem (2009) 0.94

High throughput screening for inhibitors of alpha-galactosidase. Curr Chem Genomics (2010) 0.92

A high-throughput screening assay using Krabbe disease patient cells. Anal Biochem (2012) 0.92

N4-phenyl modifications of N2-(2-hydroxyl)ethyl-6-(pyrrolidin-1-yl)-1,3,5-triazine-2,4-diamines enhance glucocerebrosidase inhibition by small molecules with potential as chemical chaperones for Gaucher disease. Bioorg Med Chem Lett (2007) 0.89

Unfolding the Therapeutic Potential of Chemical Chaperones for Age-related Macular Degeneration. Expert Rev Ophthalmol (2008) 0.89

Pharmacological enhancement of α-glucosidase by the allosteric chaperone N-acetylcysteine. Mol Ther (2012) 0.89

A Guided Tour of the Structural Biology of Gaucher Disease: Acid-β-Glucosidase and Saposin C. Enzyme Res (2011) 0.88

Celastrol increases glucocerebrosidase activity in Gaucher disease by modulating molecular chaperones. Proc Natl Acad Sci U S A (2013) 0.88

Moving towards effective therapeutic strategies for Neuronal Ceroid Lipofuscinosis. Orphanet J Rare Dis (2016) 0.88

Fabry disease - current treatment and new drug development. Curr Chem Genomics (2010) 0.85

Molecular basis of reduced glucosylceramidase activity in the most common Gaucher disease mutant, N370S. J Biol Chem (2010) 0.84

In vivo detection and quantification of chemicals that enhance protein stability. Anal Biochem (2012) 0.84

A rapid and sensitive method for measuring N-acetylglucosaminidase activity in cultured cells. PLoS One (2013) 0.84

Progress and potential of non-inhibitory small molecule chaperones for the treatment of Gaucher disease and its implications for Parkinson disease. Expert Rev Proteomics (2016) 0.83

Enzyme enhancers for the treatment of Fabry and Pompe disease. Mol Ther (2014) 0.82

Optimal therapy in Gaucher disease. Ther Clin Risk Manag (2010) 0.82

Phenylalanine hydroxylase misfolding and pharmacological chaperones. Curr Top Med Chem (2012) 0.81

Chaperone therapy for Krabbe disease: potential for late-onset GALC mutations. J Hum Genet (2015) 0.81

Binding of 3,4,5,6-tetrahydroxyazepanes to the acid-β-glucosidase active site: implications for pharmacological chaperone design for Gaucher disease. Biochemistry (2011) 0.79

The imaging probe development center and the production of molecular imaging probes. Curr Chem Genomics (2008) 0.79

Novel patient cell-based HTS assay for identification of small molecules for a lysosomal storage disease. PLoS One (2011) 0.79

Binding mode analyses and pharmacophore model development for stilbene derivatives as a novel and competitive class of α-glucosidase inhibitors. PLoS One (2014) 0.78

Disease models for the development of therapies for lysosomal storage diseases. Ann N Y Acad Sci (2016) 0.77

Tool compounds robustly increase turnover of an artificial substrate by glucocerebrosidase in human brain lysates. PLoS One (2015) 0.76

Design and Synthesis of Potent Quinazolines as Selective β-Glucocerebrosidase Modulators. J Med Chem (2016) 0.75

Articles cited by this

A Simple Statistical Parameter for Use in Evaluation and Validation of High Throughput Screening Assays. J Biomol Screen (1999) 32.67

Quantitative high-throughput screening: a titration-based approach that efficiently identifies biological activities in large chemical libraries. Proc Natl Acad Sci U S A (2006) 9.92

Replacement therapy for inherited enzyme deficiency--macrophage-targeted glucocerebrosidase for Gaucher's disease. N Engl J Med (1991) 6.09

Navigating chemical space for biology and medicine. Nature (2004) 3.44

Pharmacological chaperones rescue cell-surface expression and function of misfolded V2 vasopressin receptor mutants. J Clin Invest (2000) 2.78

Chemical chaperones increase the cellular activity of N370S beta -glucosidase: a therapeutic strategy for Gaucher disease. Proc Natl Acad Sci U S A (2002) 2.71

Structure of acid beta-glucosidase with pharmacological chaperone provides insight into Gaucher disease. Nat Chem Biol (2006) 2.59

Effectiveness of enzyme replacement therapy in 1028 patients with type 1 Gaucher disease after 2 to 5 years of treatment: a report from the Gaucher Registry. Am J Med (2002) 2.44

Chemical chaperones and permissive temperatures alter localization of Gaucher disease associated glucocerebrosidase variants. ACS Chem Biol (2006) 2.25

Differential assay for lysosomal alpha-galactosidases in human tissues and its application to Fabry's disease. Clin Chim Acta (1981) 2.01

The iminosugar isofagomine increases the activity of N370S mutant acid beta-glucosidase in Gaucher fibroblasts by several mechanisms. Proc Natl Acad Sci U S A (2006) 1.96

Therapeutic strategies to ameliorate lysosomal storage disorders--a focus on Gaucher disease. Cell Mol Life Sci (2006) 1.86

A contradictory treatment for lysosomal storage disorders: inhibitors enhance mutant enzyme activity. Trends Pharmacol Sci (2003) 1.81

Gaucher disease-associated glucocerebrosidases show mutation-dependent chemical chaperoning profiles. Chem Biol (2005) 1.68

Isofagomine- and 2,5-anhydro-2,5-imino-D-glucitol-based glucocerebrosidase pharmacological chaperones for Gaucher disease intervention. J Med Chem (2007) 1.58

Impaired trafficking of mutants of lysosomal glucocerebrosidase in Gaucher's disease. Int J Biochem Cell Biol (2005) 1.50

Pharmacological chaperone action on G-protein-coupled receptors. Curr Opin Pharmacol (2004) 1.45

Imino sugar inhibitors for treating the lysosomal glycosphingolipidoses. Glycobiology (2005) 1.31

Hydrophilic iminosugar active-site-specific chaperones increase residual glucocerebrosidase activity in fibroblasts from Gaucher patients. FEBS J (2006) 1.31

The efficacy of enzyme replacement therapy in patients with chronic neuronopathic Gaucher's disease. J Pediatr (2001) 1.25

A new pharmacology--drugging stressed folding pathways. Trends Mol Med (2005) 1.23

Biochemical, immunological, and cell genetic studies in glycogenosis type II. Am J Hum Genet (1978) 1.20

Substrate reduction therapy for lysosomal storage diseases. Acta Paediatr Suppl (2005) 1.16

Rational design and synthesis of highly potent beta-glucocerebrosidase inhibitors. Angew Chem Int Ed Engl (2005) 1.15

Lysosomal storage diseases: natural history and ethical and economic aspects. Mol Genet Metab (2006) 1.14

Design and synthesis of highly potent and selective pharmacological chaperones for the treatment of Gaucher's disease. Chembiochem (2006) 1.11

Enzymatic characterization of O-GlcNAcase isoforms using a fluorogenic GlcNAc substrate. Carbohydr Res (2006) 1.10

Alpha-1-C-octyl-1-deoxynojirimycin as a pharmacological chaperone for Gaucher disease. Bioorg Med Chem (2006) 1.10

Gaucher disease: Perspectives on a prototype lysosomal disease. Cell Mol Life Sci (2002) 1.09

High-throughput drug discovery: what can we expect from HTS? Drug Discov Today (2005) 1.05

Pharmacotherapeutic strategies using small molecules for the treatment of glycolipid lysosomal storage disorders. Expert Opin Pharmacother (2007) 1.04

High-throughput screening-driven lead discovery: meeting the challenges of finding new therapeutics. Curr Opin Drug Discov Devel (2005) 0.99

Current and emerging therapies for the lysosomal storage disorders. Expert Opin Emerg Drugs (2005) 0.95

Therapy for Gaucher disease: don't stop thinking about tomorrow. Mol Genet Metab (2006) 0.92

Aminocyclitols as pharmacological chaperones for glucocerebrosidase, a defective enzyme in Gaucher disease. ChemMedChem (2007) 0.92

High throughput screening in drug discovery. Clin Transl Oncol (2006) 0.89

Enzyme enhancement activity of N-octyl-beta-valienamine on beta-glucosidase mutants associated with Gaucher disease. Biochim Biophys Acta (2007) 0.89

Gene therapy for the lysosomal storage disorders. Curr Opin Mol Ther (2002) 0.89

Activity-based proteomics: enzyme chemistry redux. Curr Opin Chem Biol (2003) 0.83

Systematic analysis of large screening sets in drug discovery. Curr Drug Discov Technol (2004) 0.82

Articles by these authors

Prepublication data sharing. Nature (2009) 12.24

Quantitative high-throughput screening: a titration-based approach that efficiently identifies biological activities in large chemical libraries. Proc Natl Acad Sci U S A (2006) 9.92

Gaucher disease glucocerebrosidase and α-synuclein form a bidirectional pathogenic loop in synucleinopathies. Cell (2011) 6.23

High-throughput screening assays for the identification of chemical probes. Nat Chem Biol (2007) 4.50

The NCGC pharmaceutical collection: a comprehensive resource of clinically approved drugs enabling repurposing and chemical genomics. Sci Transl Med (2011) 3.80

Gaucher disease: mutation and polymorphism spectrum in the glucocerebrosidase gene (GBA). Hum Mutat (2008) 3.53

Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis. Nat Chem Biol (2012) 3.40

Chemical genomic profiling for antimalarial therapies, response signatures, and molecular targets. Science (2011) 3.30

Compound cytotoxicity profiling using quantitative high-throughput screening. Environ Health Perspect (2008) 3.11

Glucocerebrosidase mutations in subjects with parkinsonism. Mol Genet Metab (2004) 3.06

Identification and characterization of nonmuscle myosin II-C, a new member of the myosin II family. J Biol Chem (2003) 2.98

A high-throughput screen for aggregation-based inhibition in a large compound library. J Med Chem (2007) 2.97

Improving the human hazard characterization of chemicals: a Tox21 update. Environ Health Perspect (2013) 2.95

Identification of oxadiazoles as new drug leads for the control of schistosomiasis. Nat Med (2008) 2.90

Reduced glucocerebrosidase is associated with increased α-synuclein in sporadic Parkinson's disease. Brain (2014) 2.74

Fluorescence spectroscopic profiling of compound libraries. J Med Chem (2008) 2.53

Characterization of chemical libraries for luciferase inhibitory activity. J Med Chem (2008) 2.53

High-throughput combinatorial screening identifies drugs that cooperate with ibrutinib to kill activated B-cell-like diffuse large B-cell lymphoma cells. Proc Natl Acad Sci U S A (2014) 2.50

Neuropathology provides clues to the pathophysiology of Gaucher disease. Mol Genet Metab (2004) 2.46

DISC1 (Disrupted-In-Schizophrenia 1) is a centrosome-associated protein that interacts with MAP1A, MIPT3, ATF4/5 and NUDEL: regulation and loss of interaction with mutation. Hum Mol Genet (2003) 2.39

A multicenter study of glucocerebrosidase mutations in dementia with Lewy bodies. JAMA Neurol (2013) 2.32

Caenorhabditis elegans functional orthologue of human protein h-mucolipin-1 is required for lysosome biogenesis. Proc Natl Acad Sci U S A (2004) 2.28

Glucocerebrosidase mutations in Chinese subjects from Taiwan with sporadic Parkinson disease. Mol Genet Metab (2007) 2.21

Mechanism of PTC124 activity in cell-based luciferase assays of nonsense codon suppression. Proc Natl Acad Sci U S A (2009) 2.18

Compound Management for Quantitative High-Throughput Screening. JALA Charlottesv Va (2008) 2.11

A specific mechanism for nonspecific activation in reporter-gene assays. ACS Chem Biol (2008) 2.08

Discovery of a 2,4-diamino-7-aminoalkoxyquinazoline as a potent and selective inhibitor of histone lysine methyltransferase G9a. J Med Chem (2009) 1.92

A robotic platform for quantitative high-throughput screening. Assay Drug Dev Technol (2008) 1.90

Glucocerebrosidase gene mutations: a risk factor for Lewy body disorders. Arch Neurol (2008) 1.89

The spectrum of parkinsonian manifestations associated with glucocerebrosidase mutations. Arch Neurol (2008) 1.87

Illuminating insights into firefly luciferase and other bioluminescent reporters used in chemical biology. Chem Biol (2010) 1.83

Comprehensive mechanistic analysis of hits from high-throughput and docking screens against beta-lactamase. J Med Chem (2008) 1.81

Reciprocal and nonreciprocal recombination at the glucocerebrosidase gene region: implications for complexity in Gaucher disease. Am J Hum Genet (2003) 1.81

Using peripheral blood mononuclear cells to determine a gene expression profile of acute ischemic stroke: a pilot investigation. Circulation (2005) 1.79

Apparent activity in high-throughput screening: origins of compound-dependent assay interference. Curr Opin Chem Biol (2010) 1.76

Microscale thermophoresis quantifies biomolecular interactions under previously challenging conditions. Methods (2012) 1.75

Phenotypic continuum in neuronopathic Gaucher disease: an intermediate phenotype between type 2 and type 3. J Pediatr (2003) 1.75

Protein lysine methyltransferase G9a inhibitors: design, synthesis, and structure activity relationships of 2,4-diamino-7-aminoalkoxy-quinazolines. J Med Chem (2010) 1.73

Glucocerebrosidase mutations are also found in subjects with early-onset parkinsonism from Venezuela. Mov Disord (2006) 1.72

Exploring the link between glucocerebrosidase mutations and parkinsonism. Trends Mol Med (2011) 1.71

Quantitative high-throughput screening identifies 8-hydroxyquinolines as cell-active histone demethylase inhibitors. PLoS One (2010) 1.71

Complete screening for glucocerebrosidase mutations in Parkinson disease patients from Portugal. Neurobiol Aging (2007) 1.67

Molecular basis for the high-affinity binding and stabilization of firefly luciferase by PTC124. Proc Natl Acad Sci U S A (2010) 1.64

Toxicity testing in the 21st century: implications for human health risk assessment. Risk Anal (2008) 1.64

Glucocerebrosidase is present in α-synuclein inclusions in Lewy body disorders. Acta Neuropathol (2010) 1.63

Small-molecule agonists for the thyrotropin receptor stimulate thyroid function in human thyrocytes and mice. Proc Natl Acad Sci U S A (2009) 1.61

Evaluation of substituted N,N'-diarylsulfonamides as activators of the tumor cell specific M2 isoform of pyruvate kinase. J Med Chem (2010) 1.61

Cree leukoencephalopathy and CACH/VWM disease are allelic at the EIF2B5 locus. Ann Neurol (2002) 1.60

Quantitative high-throughput screen identifies inhibitors of the Schistosoma mansoni redox cascade. PLoS Negl Trop Dis (2008) 1.58

Chemical genomics profiling of environmental chemical modulation of human nuclear receptors. Environ Health Perspect (2011) 1.57

A grid algorithm for high throughput fitting of dose-response curve data. Curr Chem Genomics (2010) 1.56

Analysis of eight oil spill dispersants using rapid, in vitro tests for endocrine and other biological activity. Environ Sci Technol (2010) 1.54

Complementarity between a docking and a high-throughput screen in discovering new cruzain inhibitors. J Med Chem (2010) 1.54

Genetic mapping of targets mediating differential chemical phenotypes in Plasmodium falciparum. Nat Chem Biol (2009) 1.52