Inhibitors | Comment | Organism | Structure |
---|---|---|---|
1-hydroxy-3-(3-methylbutyl)-7-(2-phenylethyl)-3,7-dihydro-1H-purine-2,6-dione | - |
Homo sapiens | |
1-hydroxy-3-methyl-7-(2-phenylethyl)-3,7-dihydro-1H-purine-2,6-dione | - |
Homo sapiens | |
1-hydroxy-3-nonyl-7-(2-phenylethyl)-3,7-dihydro-1H-purine-2,6-dione | - |
Homo sapiens | |
1-hydroxy-3-pentyl-7-(2-phenylethyl)-3,7-dihydro-1H-purine-2,6-dione | - |
Homo sapiens | |
1-hydroxy-3-[(morpholin-4-yl)methyl]-7-(2-phenylethyl)-3,7-dihydro-1H-purine-2,6-dione | - |
Homo sapiens | |
1-hydroxy-7-(2-phenylethyl)-3,7-dihydro-1H-purine-2,6-dione | - |
Homo sapiens | |
1-hydroxy-7-(2-phenylethyl)-3-(3-phenylpropyl)-3,7-dihydro-1H-purine-2,6-dione | - |
Homo sapiens | |
1-hydroxy-7-(phenoxymethyl)-3,7-dihydro-1H-purine-2,6-dione | - |
Homo sapiens | |
1-hydroxy-7-(pyridin-2-yl)-3,7-dihydro-1H-purine-2,6-dione | - |
Homo sapiens | |
1-hydroxy-7-(pyridin-3-yl)-3,7-dihydro-1H-purine-2,6-dione | - |
Homo sapiens | |
1-hydroxy-7-(pyridin-4-yl)-3,7-dihydro-1H-purine-2,6-dione | - |
Homo sapiens | |
1-hydroxy-7-phenyl-3,7-dihydro-1H-purine-2,6-dione | - |
Homo sapiens | |
1-hydroxy-7-[(pyridin-2-yl)methyl]-3,7-dihydro-1H-purine-2,6-dione | - |
Homo sapiens | |
1-hydroxy-7-[(thiophen-2-yl)methyl]-3,7-dihydro-1H-purine-2,6-dione | - |
Homo sapiens | |
3-benzyl-1-hydroxy-7-(2-phenylethyl)-3,7-dihydro-1H-purine-2,6-dione | - |
Homo sapiens | |
3-decyl-1-hydroxy-7-(2-phenylethyl)-3,7-dihydro-1H-purine-2,6-dione | - |
Homo sapiens | |
3-dodecyl-1-hydroxy-7-(2-phenylethyl)-3,7-dihydro-1H-purine-2,6-dione | - |
Homo sapiens | |
3-ethyl-1-hydroxy-7-(2-phenylethyl)-3,7-dihydro-1H-purine-2,6-dione | - |
Homo sapiens | |
3-hydroxy-6,7,8,9-tetrahydropyrido[2,1-f]purine-2,4(1H,3H)-dione | - |
Homo sapiens | |
3-[2-(dimethylamino)ethyl]-1-hydroxy-7-(2-phenylethyl)-3,7-dihydro-1H-purine-2,6-dione | - |
Homo sapiens | |
6-hydroxy-1-(2-phenylethyl)-1,4-dihydro-5H-imidazo[4,5-b]pyridin-5-one | - |
Homo sapiens | |
7-(2-butoxyethyl)-1-hydroxy-3,7-dihydro-1H-purine-2,6-dione | - |
Homo sapiens | |
7-benzyl-1-hydroxy-3,7-dihydro-1H-purine-2,6-dione | - |
Homo sapiens | |
7-benzyl-1-[(prop-2-en-1-yl)oxy]-3,7-dihydro-1H-purine-2,6-dione | - |
Homo sapiens | |
7-benzyl-3,7-dihydro-1H-purine-2,6-dione | - |
Homo sapiens | |
additional information | discovery, synthesis and biochemical profiling of purine-2,6-dione derivatives as inhibitors of the human poly(A)-selective ribonuclease Caf1. Possible interaction modes of 3-hydroxy-pyrimidine-2,4-dione compounds with two divalent metal ions in the active site of Caf1, overview | Homo sapiens | |
NSC-104148 | - |
Homo sapiens | |
NSC-116567 | - |
Homo sapiens | |
NSC-193557 | - |
Homo sapiens | |
NSC-85703 | - |
Homo sapiens | |
NSC-86353 | substitution of the benzyl moiety with a methyl group at the N7 position (NSC-85703) reduces the inhibitory activity over 10fold | Homo sapiens |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Mg2+ | two Mg2+ ions present in the active sites of the ribonucleases of multi-subunit Ccr4-Not deadenylase and are required for RNA cleavage | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | Homo sapiens | shortening of the poly(A) tail is performed by the multi-subunit Ccr4-Not deadenylase, which contains the Caf1 (Pop2) and Ccr4 catalytic components, and poly(A)-specific ribonuclease (PARN) | ? | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | O95453 | - |
- |
Homo sapiens | Q9UIV1 | - |
- |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | shortening of the poly(A) tail is performed by the multi-subunit Ccr4-Not deadenylase, which contains the Caf1 (Pop2) and Ccr4 catalytic components, and poly(A)-specific ribonuclease (PARN) | Homo sapiens | ? | - |
? |
Synonyms | Comment | Organism |
---|---|---|
BTG1-binding factor 1 | UniProt | Homo sapiens |
Caf1 | - |
Homo sapiens |
CCR4-associated factor 1 | UniProt | Homo sapiens |
CCR4-NOT transcription complex subunit 7 | UniProt | Homo sapiens |
PARN | - |
Homo sapiens |
poly(A)-selective ribonuclease | - |
Homo sapiens |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.00059 | - |
pH and temperature not specified in the publication | Homo sapiens | 3-[2-(dimethylamino)ethyl]-1-hydroxy-7-(2-phenylethyl)-3,7-dihydro-1H-purine-2,6-dione | |
0.0015 | - |
pH and temperature not specified in the publication | Homo sapiens | 7-benzyl-1-hydroxy-3,7-dihydro-1H-purine-2,6-dione | |
0.0017 | - |
pH and temperature not specified in the publication | Homo sapiens | 1-hydroxy-3-(3-methylbutyl)-7-(2-phenylethyl)-3,7-dihydro-1H-purine-2,6-dione | |
0.0021 | - |
pH and temperature not specified in the publication | Homo sapiens | 1-hydroxy-7-(2-phenylethyl)-3-(3-phenylpropyl)-3,7-dihydro-1H-purine-2,6-dione | |
0.0036 | - |
pH and temperature not specified in the publication | Homo sapiens | 1-hydroxy-7-[(thiophen-2-yl)methyl]-3,7-dihydro-1H-purine-2,6-dione | |
0.004 | - |
pH and temperature not specified in the publication | Homo sapiens | 1-hydroxy-7-[(pyridin-2-yl)methyl]-3,7-dihydro-1H-purine-2,6-dione | |
0.0048 | - |
pH and temperature not specified in the publication | Homo sapiens | 1-hydroxy-3-pentyl-7-(2-phenylethyl)-3,7-dihydro-1H-purine-2,6-dione | |
0.0066 | - |
pH and temperature not specified in the publication | Homo sapiens | 1-hydroxy-7-(pyridin-3-yl)-3,7-dihydro-1H-purine-2,6-dione | |
0.0087 | - |
pH and temperature not specified in the publication | Homo sapiens | 1-hydroxy-3-[(morpholin-4-yl)methyl]-7-(2-phenylethyl)-3,7-dihydro-1H-purine-2,6-dione | |
0.0093 | - |
pH and temperature not specified in the publication | Homo sapiens | 1-hydroxy-3-methyl-7-(2-phenylethyl)-3,7-dihydro-1H-purine-2,6-dione | |
0.0099 | - |
pH and temperature not specified in the publication | Homo sapiens | 1-hydroxy-3-nonyl-7-(2-phenylethyl)-3,7-dihydro-1H-purine-2,6-dione | |
0.0104 | - |
pH and temperature not specified in the publication | Homo sapiens | 1-hydroxy-7-phenyl-3,7-dihydro-1H-purine-2,6-dione | |
0.0106 | - |
pH and temperature not specified in the publication | Homo sapiens | 1-hydroxy-7-(phenoxymethyl)-3,7-dihydro-1H-purine-2,6-dione | |
0.0106 | - |
pH and temperature not specified in the publication | Homo sapiens | 1-hydroxy-7-(pyridin-2-yl)-3,7-dihydro-1H-purine-2,6-dione | |
0.0122 | - |
pH and temperature not specified in the publication | Homo sapiens | 3-ethyl-1-hydroxy-7-(2-phenylethyl)-3,7-dihydro-1H-purine-2,6-dione | |
0.0133 | - |
pH and temperature not specified in the publication | Homo sapiens | 1-hydroxy-7-(2-phenylethyl)-3,7-dihydro-1H-purine-2,6-dione | |
0.0145 | - |
pH and temperature not specified in the publication | Homo sapiens | 3-benzyl-1-hydroxy-7-(2-phenylethyl)-3,7-dihydro-1H-purine-2,6-dione | |
0.0151 | - |
pH and temperature not specified in the publication | Homo sapiens | 6-hydroxy-1-(2-phenylethyl)-1,4-dihydro-5H-imidazo[4,5-b]pyridin-5-one | |
0.0206 | - |
pH and temperature not specified in the publication | Homo sapiens | 7-(2-butoxyethyl)-1-hydroxy-3,7-dihydro-1H-purine-2,6-dione | |
0.0207 | - |
pH and temperature not specified in the publication | Homo sapiens | 3-decyl-1-hydroxy-7-(2-phenylethyl)-3,7-dihydro-1H-purine-2,6-dione | |
0.0228 | - |
pH and temperature not specified in the publication | Homo sapiens | NSC-86353 | |
0.0233 | - |
pH and temperature not specified in the publication | Homo sapiens | 1-hydroxy-7-(pyridin-4-yl)-3,7-dihydro-1H-purine-2,6-dione | |
0.0239 | - |
pH and temperature not specified in the publication | Homo sapiens | 3-[2-(dimethylamino)ethyl]-1-hydroxy-7-(2-phenylethyl)-3,7-dihydro-1H-purine-2,6-dione | |
0.0282 | - |
pH and temperature not specified in the publication | Homo sapiens | 3-hydroxy-6,7,8,9-tetrahydropyrido[2,1-f]purine-2,4(1H,3H)-dione | |
0.0287 | - |
pH and temperature not specified in the publication | Homo sapiens | NSC-116567 | |
0.0295 | - |
pH and temperature not specified in the publication | Homo sapiens | 3-dodecyl-1-hydroxy-7-(2-phenylethyl)-3,7-dihydro-1H-purine-2,6-dione | |
0.0386 | - |
pH and temperature not specified in the publication | Homo sapiens | NSC-104148 | |
0.0841 | - |
pH and temperature not specified in the publication | Homo sapiens | 1-hydroxy-7-phenyl-3,7-dihydro-1H-purine-2,6-dione | |
0.119 | - |
pH and temperature not specified in the publication | Homo sapiens | 1-hydroxy-7-(pyridin-2-yl)-3,7-dihydro-1H-purine-2,6-dione | |
0.125 | - |
pH and temperature not specified in the publication | Homo sapiens | 1-hydroxy-7-(pyridin-3-yl)-3,7-dihydro-1H-purine-2,6-dione | |
0.245 | - |
pH and temperature not specified in the publication | Homo sapiens | 1-hydroxy-7-(pyridin-4-yl)-3,7-dihydro-1H-purine-2,6-dione | |
0.251 | - |
pH and temperature not specified in the publication | Homo sapiens | NSC-85703 | |
0.525 | - |
pH and temperature not specified in the publication | Homo sapiens | NSC-193557 | |
1 | - |
above, pH and temperature not specified in the publication | Homo sapiens | 7-benzyl-1-[(prop-2-en-1-yl)oxy]-3,7-dihydro-1H-purine-2,6-dione | |
1 | - |
above, pH and temperature not specified in the publication | Homo sapiens | 7-benzyl-3,7-dihydro-1H-purine-2,6-dione |
General Information | Comment | Organism |
---|---|---|
physiological function | in eukaryotic cells, cytoplasmic mRNA is characterized by the presence of a 3' poly(A) tail. The median length of the tail varies from 27 to 28 nucleotides in yeast to 60-100 nucleotides in mammalian cells.The tail is important for the control of gene expression, enzymatic shortening of the poly(A) tail (deadenylation) can initiate mRNA degradation and repress translation. An important enzyme involved in cytoplasmic deadenylation is the multi-component Ccr4-Not complex. In addition to six noncatalytic subunits, the complex contains two subunits with ribonuclease activity: both Caf1 and Ccr4 display Mg2+-dependent 3'-'-5' exoribonuclease activity with a preference for poly(A). While the enzymatic activity of Caf1 is associated with an RNAse D/DEDD (Asp-Glu-Asp-Asp) domain, the enzymatic activity of Ccr4 is provided by an EEP (endonuclease-exonuclease-phosphatase) domain | Homo sapiens |