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(3E)-1-(3,4-dichlorobenzyl)-4-methoxy-5-phenyl-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0061 mM
(3E)-1-(3,4-dichlorobenzyl)-5-iodo-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.00094 mM; IC50: 0.016 mM
(3E)-1-(3,4-dichlorobenzyl)-5-methoxy-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0029 mM
(3E)-1-{2-bromo-2-[3-(trifluoromethyl)phenyl]ethyl}-5-chloro-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0095 mM
(3E)-3-[(acetyloxy)imino]-1-(3,4-dichlorobenzyl)-2-oxoindoline-5-carbonitrile
-
IC50: 0.012 mM
(3E)-3-[(acetyloxy)imino]-1-(3,4-dichlorobenzyl)-2-oxoindoline-5-carboxamide
-
IC50: 0.0041 mM
(3E)-3-[(acetyloxy)imino]-1-(3,4-dichlorobenzyl)-2-oxoindoline-5-carboxylic acid
-
IC50: 0.05 mM
(3E)-5-(trifluoromethoxy)-1-[3-(trifluoromethyl)benzyl]-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0034 mM
(3E)-5-(trifluoromethoxy)-1-[3-(trifluoromethyl)benzyl]-1H-indole-2,3-dione 3-oxime
-
IC50: 0.078 mM
(3E)-5-bromo-1-(3,4-dichlorobenzyl)-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.00081 mM
(3E)-5-chloro-1-(2,3-dichlorobenzyl)-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0027 mM
(3E)-5-chloro-1-(2,4-dichlorobenzyl)-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0012 mM
(3E)-5-chloro-1-(2,5-dichlorobenzyl)-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.00088 mM
(3E)-5-chloro-1-(2-chloro-5-fluorobenzyl)-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0065 mM
(3E)-5-chloro-1-(2-naphthylmethyl)-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.014 mM
(3E)-5-chloro-1-(2-phenylethyl)-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.019 mM
(3E)-5-chloro-1-(3,4-dichlorobenzyl)-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0018 mM; IC50: 0.017 mM
(3E)-5-chloro-1-(3,5-dichlorobenzyl)-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0013 mM
(3E)-5-chloro-1-(3-chloro-4-methoxybenzyl)-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.021 mM
(3E)-5-chloro-1-(3-methoxybenzyl)-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.013 mM
(3E)-5-chloro-1-(4-chlorobenzyl)-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.012 mM
(3E)-5-chloro-1-(4-methoxybenzyl)-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.052 mM
(3E)-5-chloro-1-[2-(3,4-dichlorophenoxy)ethyl]-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0062 mM
(3E)-5-chloro-1-[2-(3,4-dichlorophenyl)ethyl]-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0013 mM
(3E)-5-chloro-1-[2-(trifluoromethyl)benzyl]-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.018 mM
(3E)-5-chloro-1-[2-(trifluoromethyl)benzyl]-1H-indole-2,3-dione 3-oxime
-
IC50: 0.321 mM
(3E)-5-chloro-1-[3-(3,4-dichlorophenyl)propyl]-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.016 mM
(3E)-5-chloro-1-[3-(trifluoromethyl)benzyl]-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.006 mM; IC50: 0.036 mM
(3E)-5-chloro-1-[3-(trifluoromethyl)benzyl]-1H-indole-2,3-dione 3-oxime
-
IC50: 0.114 mM
(3E)-5-chloro-1-[4-(trifluoromethyl)benzyl]-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.012 mM
(3E)-5-chloro-1-[4-(trifluoromethyl)benzyl]-1H-indole-2,3-dione 3-oxime
-
IC50: 0.013 mM
(3E)-5-chloro-1-{1-[2-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0088 mM
(3E)-5-chloro-1-{1-[2-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,3-dione 3-oxime
-
IC50: 0.045 mM
(3E)-5-chloro-1-{1-[3-(trichloromethyl)phenyl]ethyl}-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0034 mM
(3E)-5-chloro-1-{1-[3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,3-dione 3-oxime
-
IC50: 0.022 mM
(3E)-5-chloro-1-{2-ethoxy-2-[3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.095 mM
(3E)-5-chloro-1-{2-hydroxy-2-[3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.019 mM
(3E)-5-chloro-1-{2-[3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0041 mM
(3E)-5-chloro-1-{2-[3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,3-dione 3-oxime
-
IC50: 0.08 mM
(3E)-5-chloro-7-methyl-1-[3-(trifluoromethyl)benzyl]-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.012 mM
(3E)-5-fluoro-1-[3-(trifluoromethyl)benzyl]-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0061 mM
(3E)-5-fluoro-1-[3-(trifluoromethyl)benzyl]-1H-indole-2,3-dione 3-oxime
-
IC50: 0.043 mM
(3E)-6-chloro-1-[3-(trifluoromethyl)benzyl]-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0058 mM
1-(1,3-benzodioxol-5-ylmethyl)-4-(4-([(4-chlorophenyl)thio]methyl)benzoyl) piperazine
slight inhibition of UCH-L1
1-(3',4'-dihydroxybenzyl)-1,2,3,4-tetrahydroisoquinoline
the enzyme is covalently modified by the endogenous parkinsonism inducing dopamine derivative. 1-(3',4'-dihydroxybenzyl)-1,2,3,4-tetrahydroisoquinoline binds UCH-L1 specifically at Cys152 in vitro. This increases the amount of insoluble UCH-L1 and reduces its hydrolase activity in SH-SY5Y cells
1-benzyl-3-hydroxy-4-(5-methyl-2-furoyl)-5-(3-pyridinyl)-1,5-dihydro-2H-pyrrol-2-one
-
is a competitive inhibitor of UCH-L3, significantly inhibits hydrolysis activity of UCH-L3 by 83.2%
15-deoxy-DELTA12,14-prostaglandin J2
-
modification of UCH-L1 by cyclopentenone prostaglandins causes unfolding and aggregation. A single thiol group on Cys152 reacts with the alpha,beta-unsaturated carbonyl center in the cyclopentenone ring of prostaglandins, resulting in a covalent adduct, spectral analysis, overview
2-([4-(2-furylmethyl)-5-(2-thienylmethyl)-4H-1,2,4-triazol-3-yl]thio)-N-(2-methoxydibenzo[b,d]furan-3-yl)acetamide
-
2-propenal
-
carbonyl modification with 0.1 mM
2-[(5-ethyl-5H-[1,2,4]triazino[5,6-b]indol-3-yl)thio]-N-(4-methyl-2-pyridinyl)acetamide
-
3,5-bis[(4-nitrophenyl)methylidene]-1-prop-2-enoylpiperidin-4-one
i.e. b-AP15, administration of the UCHL5 inhibitor reduces the expression of FN, type I collagen, Smad2/Smad3, and the deposition of collagen in lung tissues in a bleomycin-induced model of pulmonary fibrosis
3-amino-2-(4-methylbenzoyl)-6-oxo-6,7-dihydrothieno[2,3-b]pyridine-5-carboxylaic acid
-
an uncompetitive inhibitor of UCHL1 that binds only to the Michaelis complex and not to free enzyme
3-amino-2-(cyclohexylcarbonyl)-6-oxo-6,7-dihydrothieno[2,3-b]pyridine-5-carboxylic acid
-
-
3-amino-2-keto-7Hthieno[2,3-b]pyridin-6-one derivative
-
-
3-amino-2-[(2-methoxyphenyl)carbonyl]-6-oxo-6,7-dihydrothieno[2,3-b]pyridine-5-carboxylic acid
-
-
3-amino-2-[(4-chlorophenyl)carbonyl]-6-oxo-6,7-dihydrothieno[2,3-b]pyridine-5-carboxylic acid
-
-
3-amino-2-[(4-methylphenyl)carbonyl]-6-oxo-6,7-dihydrothieno[2,3-b]pyridine-5-carboxylic acid
-
-
3-amino-2-[(4-tert-butylphenyl)carbonyl]-6-oxo-6,7-dihydrothieno[2,3-b]pyridine-5-carboxylic acid
-
-
3-amino-2-[(naphthalen-1-yloxy)carbonyl]-6-oxo-6,7-dihydrothieno[2,3-b]pyridine-5-carboxylic acid
-
-
3-amino-2-[(naphthalen-2-yloxy)carbonyl]-6-oxo-6,7-dihydrothieno[2,3-b]pyridine-5-carboxylic acid
-
-
3-amino-6-oxo-2-[[4-(trifluoromethyl)phenyl]carbonyl]-6,7-dihydrothieno[2,3-b]pyridine-5-carboxylic acid
-
-
3-hydroxy-5-(4-methoxyphenyl)-1-(1,3,4-thiadiazol-2-yl)-4-(2-thienylcarbonyl)-1,5-dihydro-2H-pyrrol-2-one
-
significantly inhibits hydrolysis activity of UCH-L3 by 76.5%
3-[4-methyl-5-(([3-(2-thienyl)-1,2,4-oxadiazol-5-yl]methyl)thio)-4H-1,2,4-triazol-3-yl]-1H-indole
-
inhibits hydrolysis activity by 16.2%
4,5,6,7-tetrachloroindan-1,3-dione
-
UCH-L3 inhibition reduces epithelial sodium channel currents, decreases apical membrane epithelial sodium channel expression and increases epithelial sodium channel ubiquitination at the apical surface
4-([benzyl(methyl)amino]sulfonyl)-N-[5-(benzylthio)-1,3,4-thiadiazol-2-yl]benzamide
-
4-hydroxy-2-hexenal
-
carbonyl modification in a dose-dependent manner
4-hydroxy-2-nonenal
-
carbonyl modification with 0.01-0.1 mM leads to decreased ubiquitin binding, and both increased insolubility and interactions with proteins over 30 kDa compared with the wild-type
5-(4-fluorophenyl)-3-hydroxy-4-(5-methyl-2-furoyl)-1-(3-pyridinylmethyl)-1,5-dihydro-2H-pyrrol-2-one
-
significantly inhibits hydrolysis activity of UCH-L3 by 76.8%
5-chloro-1-(3,4-dichlorobenzyl)-1H-indole-2,3-dione 3-(O-acetyloxime)
-
IC50: 0.0018 mM
5-chloro-1-(3,4-dichlorobenzyl)-1H-indole-2,3-dione 3-oxime
-
IC50: 0.012 mM
8-[(1H-benzimidazol-2-ylmethyl)sulfanyl]-2,2-dimethyl-5-(morpholin-4-yl)-1,4-dihydro-2H-pyrano[4'',3'':4',5']pyrido[3',2':4,5]thieno[3,2-d]pyrimidine
-
aldehyde product of fatty acid peroxidation
i.e. HNE; modifies isozyme L1 at physiological concentrations of 0.01-0.1 mM and reduces enzyme activity, excess N-acetyl-L-cysteine protects
-
amyloid beta
30% inhibition
-
Antibody
-
anti-UCH antibodies increase the rate of polyspermy during in vitro fertilization by reducing UCH enzymatic activity
-
benzyloxycarbonyl-Val-Ala-Glu(gamma-methoxy) fluoromethylketone
co-crystal structure reveals that the inhibitor binds in the active-site cleft, irreversibly modifying the active-site cysteine
Ca2+
-
59% inhibition at 5 mM
dimethyl sulfoxide
-
catalytic activity decreases slightly with increasing dimethyl sulfoxide concentrations. At 2% (v/v) dimethyl sulfoxide, the proteolytic activity of UCH-L3 is reduced by ca. 5% in comparison to dimethyl sulfoxide-free conditions
DTT
-
erythrocyte isozyme ISOT-S and ISOT-L, inhibition by chelating of Zn2+
epoxysuccinyl-leucylamido-(4-guanidino) butane
reduces UCH-L1 mRNA, protein level and activity. Caspase-mediated apoptosis in epoxysuccinyl-leucylamido-(4-guanidino) butane-treated fibroblasts is reversed by transfection with a UCH-L1 plasmid
isatin O-acyl oximes
-
reversible and competitive inhibition, inhibitory potency and features of the drivatives, specific inhibition of UCH-L1, poor inhibition of UCH-L3, IC50 values, overview
J series prostaglandins
-
inhibition of the enzyme is involved in disruption of the proteasome pathway and leads to apoptosis
-
KCl
-
92% inhibition at 0.2 M
LDN 57 444
UCH-L1 inhibition leads to a time and concentration-dependent formation of membrane protrusions, accompanied by redistribution of alpha-actinin-4 to the membrane. Expression level of alpha-actinin-4 remains stable, whereas the beta-catenin content increases. Inhibition of UCH-L1 does not induce apoptosis
Mg2+
-
61% inhibition at 5 mM
N,N'-(oxydi-4,1-phenylene)dibenzenesulfonamide
slight inhibition of UCH-L1
N,N'-4,4'-biphenyldiylbis(4-ethylbenzenesulfonamide)
strong inhibition of UCH-L1
N-(2-[(6,7-dimethoxy-1-isoquinolinyl)methyl]-4,5-dimethoxyphenyl)-4-(2-oxo-1-pyrrolidinyl)benzenesulfonamide
slight inhibition of UCH-L1
N-(3,6-dichloro-2-pyridinyl)-N'-([(4,6-diphenyl-2-pyrimidinyl)amino]carbonyl)sulfamide
-
N-(4-([(4-ethoxyphenyl)amino]sulfonyl)phenyl)-2-naphthalenesulfonamide
slight inhibition of UCH-L1
N-(4-([(4-methylphenyl)amino]sulfonyl)phenyl)-2-phenyl-2-(phenylthio)acetamide
slight inhibition of UCH-L1
N-[2-(4-benzyl-1-piperazinyl)-2-oxoethyl]-N-(3-methylphenyl)benzenesulfonamide
slight inhibition of UCH-L1
oligomeric Abeta
-
treatment of hippocampal slices produces a deficit in long term potentiation. Effect can be reversed by coadministering a recombinant UCH-L1 protein
-
peptides
-
containing either of the cleavage site sequence found in ubiquitin polymers, but not unrelated peptides
tosyl-L-phenylalanine chloromethyl ketone
inhibits fragmentation of AT-3 carrying six consecutive glutamines
ubiquitin vinyl methyl ester
a ubiquitin-based suicide substrate, binding structure analysis with wild-type and mutant S18Y enzymes, overview
-
ubiquitin vinylmethyl ester
inhibitor forms a covalent adduct with the active site cysteine of the enzyme
-
ubiquitin vinylsulfone
irreversible inhibitor that covalently modifies the active-site cysteines of DUBs
-
iodoacetamide
-
-
iodoacetamide
-
Cys-residue for catalysis
iodoacetamide
-
is a non-competitive inhibitor of UCH-L3
iodoacetamide
-
prevents deubiquitination
LDN-57444
-
a reversible, competitive, active site-directed isatin oxime with consistent preference for UCHL1 over UCHL3 by 28fold
LDN-57444
reversible, competitive, active site-directed isatin oxime, 70% inhibition with 0.005 mM
LDN-57444
-
i.e. 3-(O-acetyloxime), 5-chloro-1-[(2,5-dichlorophenyl)methyl]-1H-indole-2,3-dione
Mn2+
-
-
Mn2+
-
98% inhibition at 5 mM
N-ethylmaleimide
-
UCH-8
RNAi
-
knockdown of UCHL1, leads to short lifespan of animals and earlier accumulation of aging specific lipofucsin with increasing age when compared with the wild-type
-
RNAi
-
knockdown of UCH37, abolishes TGF-beta-dependent transcriptional responses
-
RNAi
knockdown of UCH-L1, inhibits the proliferation of BL cells in suspension and semisolid agar and activates strong LFA-1 dependent homotypic adhesion
-
RNAi
suppressing UCH-L1 expression by RNAi significantly suppresses the invasion in vitro and in vivo, and the activation of Akt and downstream mitogen activates protein kinases c-Jun N-terminal kinases and p38, but not ERK
-
siRNA
-
knockdown of UCHL1 by small interfering RNA results in increased nuclear factor-kappa B activity in A7r5 cells
-
siRNA
inhibits the expression of UCH-L1 in normal control fibroblasts, followed by a remarkable increase of apoptosis both in the presence and in the absence of epoxysuccinyl-leucylamido-(4-guanidino) butane. UCH-L1 siRNA 14311 almost completely inhibits synthesis of UCH-L1 protein in about 70% of cells and reduces the UCH-L1 mRNA level more then 7fold
-
siRNA
stabilization of HCF-1 through depletion of Bap1. Knockdown of Bap1 results in a modest increase in the steady-state levels of HCF-1, which presumably helps to promote the transition from G1 into S-phase
-
siRNA
-
knockdown of UCH-L3 leads to a decrease of epithelial sodium channel currents
-
ubiquitin
-
product inhibition
ubiquitin
-
free ubiquitin acts as a specific, competitive, noncovalent inhibitor
ubiquitin
increasing ubiquitin concentrationin reveals a decrease in the cleavage efficiency, presumably as a result of competition between the second (substrate) ubiquitin molecule and the fluorigenic substrate binding to the enzyme active centre; increasing ubiquitin concentrationin reveals a decrease in the cleavage efficiency, presumably as a result of competition between the second (substrate) ubiquitin molecule and the fluorigenic substrate binding to the enzyme active centre. In the case of OTU-1 full-length ubiquitin does not result in any substantial decrease or increase of the processing of the fluorigenic substrate; increasing ubiquitin concentrationin reveals a decrease in the cleavage efficiency, presumably as a result of competition between the second (substrate) ubiquitin molecule and the fluorigenic substrate binding to the enzyme active centre. In the case of UCH-L3 inhibition of the fluorigenic substrate by elevated concentrations of full-length ubiquitin
ubiquitin
-
submicromolar concentrations activate while higher concentrations inhibit the enzyme, regulatory function, 2-step inhibition mechanism via 2 ubiquitin binding sites extending the active site
Ubiquitin aldehyde
-
-
-
Ubiquitin aldehyde
-
carboxy-terminal aldehyde of ubiquitin
-
Ubiquitin aldehyde
-
UCH-8
-
Ubiquitin aldehyde
inhibition mechanism
-
Ubiquitin aldehyde
-
inhibition in absence of ubiquitin, competitive to ubiquitin
-
Ubiquitin aldehyde
-
specific nonpermeating UCH inhibitor, signficantly increases rates of sperm-zona pellucida penetration and polyspermy during in vitro fertilization by reducing UCH enzymatic activity in motile boar spermatozoa. Ipase-T and ubiquitin aldehyde cancel each other out when added concomitantly to the fertilization medium
-
Ubiquitin aldehyde
-
specific inhibitor for UCH, partly inhibits maturation of ubiquitin precursor derivative in living oocytes
-
ubiquitin-aldehyde
-
-
additional information
-
phenylmethylsulfonyl fluoride does not affect significantly the UCH-enzyme activity
-
additional information
-
not inhibited by phenylmethylsulfonyl fluoride, 1,10-phenanthroline
-
additional information
-
no inhibition by PMSF, EDTA, and o-phenanthroline
-
additional information
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IC50 above 0.1 mM: (3E)-5-chloro-1-(pyridin-3-ylmethyl)-1H-indole-2,3-dione 3-(O-acetyloxime), (3E)-5-chloro-1-(pyridin-4-ylmethyl)-1H-indole-2,3-dione 3-(O-acetyloxime), 4-({(3E)-3-[(acetyloxy)imino]-5-chloro-2-oxo-2,3-dihydro-1H-indol-1-yl}methyl)benzoic acid
-
additional information
-
the enzyme is inhibited by zinc-chelating agents
-
additional information
-
not inhibited by N1-cyclopropyl-N2-(4-methoxyphenyl)-N2-[(4-methylphenyl)sulfonyl]glycinamide, N-(3-[1-acetyl-5-(2-thienyl)-4,5-dihydro-1H-pyrazol-3-yl]phenyl)ethanesulfonamide, N1-cyclopropyl-N2-[(4-methoxyphenyl)sulfonyl]-N2-(4-methylphenyl)glycinamide, N1-cyclopentyl-N2-(3-methoxyphenyl)-N2-(phenylsulfonyl)glycinamide and 4-(([5-(2-furyl)-4-phenyl-4H-1,2,4-triazol-3-yl]thio)methyl)-1,3-thiazol-2-amine
-
additional information
-
no carbonyl modification with 0.1 mM or 0.5 mM methylglyoxal and 0.1 mM or 0.5 mM malondialdehyde
-
additional information
-
monoubiquitination inhibits ubiquitin binding in vitro and prevents UCH-L1 from regulating free ubiquitin levels in cells involving auto-deubiquitination. Intramolecular deubiquitination, which is dependent on the hydrolytic activity of UCH-L1, regulates the lifetime of monoubiquitination, thereby affecting the cellular level of monoubiquitinated UCH-L1
-
additional information
very high sodium citrate concentrations reveal a decrease in activity; very high sodium citrate concentrations reveal a decrease in activity; very high sodium citrate concentrations reveal a decrease in activity, most dramatic for OTU-1, which is due to enzyme precipitation in the assay
-
additional information
very high sodium citrate concentrations reveal a decrease in activity; very high sodium citrate concentrations reveal a decrease in activity; very high sodium citrate concentrations reveal a decrease in activity, most dramatic for OTU-1, which is due to enzyme precipitation in the assay
-
additional information
very high sodium citrate concentrations reveal a decrease in activity; very high sodium citrate concentrations reveal a decrease in activity; very high sodium citrate concentrations reveal a decrease in activity, most dramatic for OTU-1, which is due to enzyme precipitation in the assay
-
additional information
-
very high sodium citrate concentrations reveal a decrease in activity; very high sodium citrate concentrations reveal a decrease in activity; very high sodium citrate concentrations reveal a decrease in activity, most dramatic for OTU-1, which is due to enzyme precipitation in the assay
-
additional information
in high metastatic potential clones, two isoforms of UCH-L1 are downregulated
-
additional information
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in high metastatic potential clones, two isoforms of UCH-L1 are downregulated
-
additional information
in vitro, K48-linked ubiquitin dimers pronouncedly inhibit the hydrolase activity of UCH-L3; mono-ubiquitin, a previously identified interacting protein, inhibits the hydrolase activity of UCH-L1
-
additional information
in vitro, K48-linked ubiquitin dimers pronouncedly inhibit the hydrolase activity of UCH-L3; mono-ubiquitin, a previously identified interacting protein, inhibits the hydrolase activity of UCH-L1
-
additional information
kinetics and inhibitor docking study using crystal structure data of PDB code 2ETL, overview. No or poor inhibition by 3-methyl-8-(4-methyl-1-piperazinyl)-7-(3-phenylpropyl)-3,7-dihydro-1Hpurine-2,6-dione, 1-(4-methoxyphenyl)-4-([3-(4-methoxyphenyl)-1,2,4-oxadiazol-5-yl]methyl)piperazine, N1-cyclopropyl-N2-(4-ethoxyphenyl)-N2-[(4-methylphenyl)sulfonyl]glycinamide, N-[6-((2-[(4-chlorophenyl)thio]acetyl)amino)-1,3-benzothiazol-2-yl]butanamide and N-1,3-benzothiazol-2-yl-2-([5-(4-morpholinylmethyl)-4-phenyl-4H-1,2,4-triazol-3-yl]thio)acetamide
-
additional information
-
kinetics and inhibitor docking study using crystal structure data of PDB code 2ETL, overview. No or poor inhibition by 3-methyl-8-(4-methyl-1-piperazinyl)-7-(3-phenylpropyl)-3,7-dihydro-1Hpurine-2,6-dione, 1-(4-methoxyphenyl)-4-([3-(4-methoxyphenyl)-1,2,4-oxadiazol-5-yl]methyl)piperazine, N1-cyclopropyl-N2-(4-ethoxyphenyl)-N2-[(4-methylphenyl)sulfonyl]glycinamide, N-[6-((2-[(4-chlorophenyl)thio]acetyl)amino)-1,3-benzothiazol-2-yl]butanamide and N-1,3-benzothiazol-2-yl-2-([5-(4-morpholinylmethyl)-4-phenyl-4H-1,2,4-triazol-3-yl]thio)acetamide
-
additional information
the binding of SARS-CoV covalent and non-covalent inhibitors to the SARS-CoV-2 papain-like protease and ovarian tumor domain deubiquitinases (OTUB1 and OTUB2) is studied; the binding of SARS-CoV covalent and non-covalent inhibitors to the SARS-CoV-2 papain-like protease and ovarian tumor domain deubiquitinases (OTUB1 and OTUB2) is studied
-
additional information
the binding of SARS-CoV covalent and non-covalent inhibitors to the SARS-CoV-2 papain-like protease and ovarian tumor domain deubiquitinases (OTUB1 and OTUB2) is studied; the binding of SARS-CoV covalent and non-covalent inhibitors to the SARS-CoV-2 papain-like protease and ovarian tumor domain deubiquitinases (OTUB1 and OTUB2) is studied
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additional information
-
class of 3-amino-2-keto-7H-thieno[2,3-b]pyridin-6-one derivatives are moderately potent UCH-L1 inhibitors. Carboxylate at the 5-position and the 6-pyridinone ring are necessary for inhibitory activity. Inhibitory activity is dependent on the nature of the ketone substituent at the 2-position, with 4-Me-Ph and 2-naphthyl being best. Compounds are uncompetitive inhibitors of UCH-L1, binding only to the Michaelis-complex and not to free enzyme. Active compounds are selective for UCH-L1, exhibiting no inhibition of other cysteine hydrolases or cytotoxicity in serum starved N2A cells. Not inhibited by compound 9, 17, 19, 22, 24, 27, 28, 29, 30, 32 and 33
-
additional information
-
treatment of hippocampal slices with a small-molecule inhibitor of UCH-L1 enzymatic activity produces a deficit in long term potentiation
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additional information
EDTA, HgCl2 and p-chloro-mecuribenzoate do not inhibit fragmentation of AT-3 carrying six consecutive glutamines
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additional information
magnitude of induction of uchl1 is lower in asymptomatic, 8-month old, alpha-tocopherol transfer protein deficient mice and in 8-month old mice fed an alpha-tocopherol-depleted diet
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additional information
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UCH-L1 is easily affected by redox status
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additional information
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very high sodium citrate concentrations reveal a decrease in activity. Full-length ubiquitin does not result in any substantial decrease or increase of the processing of the fluorigenic substrate
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