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Literature summary for 3.1.26.13 extracted from
- Design, synthesis and biological evaluations of N-hydroxy thienopyrimidine-2,4-diones as inhibitors of HIV reverse transcriptase-associated RNase H (2017), Eur. J. Med. Chem., 141, 149-161 .
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| recombinant expression of enzyme mutant C280S | Human immunodeficiency virus 1 |
Crystallization (Commentary)
| Crystallization (Comment) | Organism |
|---|---|
| determination and analysis of crystal structure of enzyme mutant C280S in complex with inhibitor 6-benzyl-3-hydroxythieno[2,3-d]pyrimidine-2,4(1H,3H)-dione, PDB ID 6AOC, hanging drop vapor diffusion method, mixing of 11 mg/ml protein in 10 mM MnCl2, 5 mM tris(2-carboxyethyl)phosphine (TCEP) HCl, 0.5% beta-octylglucoside, and 1 mM 6-benzyl-3-hydroxythieno[2,3-d]pyrimidine-2,4(1H,3H)-dione in a 1:1 ratio with crystallization solution containing 15% PEG 3500, 0.1 M sodium potassium phosphate, 5% ethylene glycol, and 0.1 M Tris, pH 6.5, large, blocky crystals grow at 18°C in 2-3 days, molecular replacement using structure PDB ID 4KFB as the initial search model | Human immunodeficiency virus 1 |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| 2-hydroxy-6-phenylisoquinoline-1,3(2H,4H)-dione | - |
Human immunodeficiency virus 1 |  |
| 3-hydroxy-1,5,6,7-tetrahydro-2H-cyclopenta[4,5]thieno[2,3-d]pyrimidine-2,4(3H)-dione | - |
Human immunodeficiency virus 1 | |
| 3-hydroxy-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione | - |
Human immunodeficiency virus 1 | |
| 3-hydroxy-5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione hydrobromide | - |
Human immunodeficiency virus 1 | |
| 3-hydroxy-5,6-dimethylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione | - |
Human immunodeficiency virus 1 | |
| 3-hydroxy-5-methyl-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-6-carboxylic acid | - |
Human immunodeficiency virus 1 | |
| 3-hydroxy-5-methylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione | - |
Human immunodeficiency virus 1 | |
| 3-hydroxy-5-phenylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione | - |
Human immunodeficiency virus 1 | |
| 3-hydroxy-6-phenylthieno [3,2-d]pyrimidine-2,4(1H,3H)-dione | - |
Human immunodeficiency virus 1 | |
| 3-hydroxy-6-phenylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione | - |
Human immunodeficiency virus 1 | |
| 3-hydroxy-7-phenylquinazoline-2,4(1H,3H)-dione | - |
Human immunodeficiency virus 1 | |
| 3-hydroxythieno[2,3-d]pyrimidine-2,4(1H,3H)-dione | - |
Human immunodeficiency virus 1 | |
| 5-(4-chlorophenyl)-3-hydroxythieno[2,3-d]pyrimidine-2,4(1H,3H)-dione | - |
Human immunodeficiency virus 1 | |
| 6-(4-chlorophenyl)-3-hydroxythieno[3,2-d]pyrimidine-2,4(1H,3H)-dione | - |
Human immunodeficiency virus 1 | |
| 6-(4-fluorophenyl)-3-hydroxythieno[3,2-d]pyrimidine-2,4(1H,3H)-dione | - |
Human immunodeficiency virus 1 | |
| 6-benzyl-3-hydroxythieno[2,3-d]pyrimidine-2,4(1H,3H)-dione | - |
Human immunodeficiency virus 1 | |
| 7-(4-chlorophenyl)-3-hydroxyquinazoline-2,4(1H,3H)-dione | - |
Human immunodeficiency virus 1 | |
| 7-benzyl-3-hydroxy-5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione hydrochloride | - |
Human immunodeficiency virus 1 | |
| 7-benzyl-3-hydroxyhexahydropyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione hydrochloride | - |
Human immunodeficiency virus 1 | |
| 7-ethyl-3-hydroxy-5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione hydrochloride | - |
Human immunodeficiency virus 1 | |
| additional information | design, synthesis and biological evaluations of N-hydroxy thienopyrimidine-2,4-diones as inhibitors of HIV reverse transcriptase-associated RNase H, antiviral activity, overview. The compounds potently and selectively inhibit RNase H with considerable potency against HIV-1 in cell culture. They also show inhibition of integrase strand transfer (INST) activity. Structure-activity-relationship analysis. Molecular modeling of analogues 3-hydroxy-6-phenylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione and 5-(4-chlorophenyl)-3-hydroxythieno[2,3-d]pyrimidine-2,4(1H,3H)-dione at the RNase H active site. Analysis of the enzyme's crystal structure in complex with inhibitor 6-benzyl-3-hydroxythieno[2,3-d]pyrimidine-2,4(1H,3H)-dione | Human immunodeficiency virus 1 |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| additional information | Human immunodeficiency virus 1 | HIV RNase H cleaves viral RNA at multiple stages of reverse transcription with at least three distinct modes: random internal cleavages, DNA 3' end-directed and polymerase dependent cleavages, and RNA 5' end-directed cleavages. A biochemical assay uses the HTS-1 RNA/DNA substrate to specifically probe random internal cleavage, which is believed to be the dominant mode of RNA cutting | ? | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Human immunodeficiency virus 1 | - |
HIV-1 | - |
Purification (Commentary)
| Purification (Comment) | Organism |
|---|---|
| recombinant enzyme mutant C280S | Human immunodeficiency virus 1 |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| additional information | HIV RNase H cleaves viral RNA at multiple stages of reverse transcription with at least three distinct modes: random internal cleavages, DNA 3' end-directed and polymerase dependent cleavages, and RNA 5' end-directed cleavages. A biochemical assay uses the HTS-1 RNA/DNA substrate to specifically probe random internal cleavage, which is believed to be the dominant mode of RNA cutting | Human immunodeficiency virus 1 | ? | - |
? | |
| additional information | RNA/DNA duplex substrate HTS-1 (RNA 5'-gaucugagccuggagcu-3'-fluorescein annealed to DNA 3'-CTAGACTCGGACCCTCGA-5'-dabsyl) is a high sensitivity duplex that assesses non-specific internal cleavage | Human immunodeficiency virus 1 | ? | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| HIV reverse transcriptase-associated RNase H | - |
Human immunodeficiency virus 1 |
| HIV RNase H | - |
Human immunodeficiency virus 1 |
| HIV RT-associated RNase H | - |
Human immunodeficiency virus 1 |
| human immunodeficiency virus reverse transcriptase-associated RNase H | - |
Human immunodeficiency virus 1 |
| human immunodeficiency virus RT-associated RNase H | - |
Human immunodeficiency virus 1 |
| RT RNase H | - |
Human immunodeficiency virus 1 |
IC50 Value
| IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
|---|---|---|---|---|---|
| 0.00004 | - |
pH and temperature not specified in the publication | Human immunodeficiency virus 1 | 5-(4-chlorophenyl)-3-hydroxythieno[2,3-d]pyrimidine-2,4(1H,3H)-dione | |
| 0.000043 | - |
pH and temperature not specified in the publication | Human immunodeficiency virus 1 | 6-benzyl-3-hydroxythieno[2,3-d]pyrimidine-2,4(1H,3H)-dione | |
| 0.00007 | - |
pH and temperature not specified in the publication | Human immunodeficiency virus 1 | 6-(4-chlorophenyl)-3-hydroxythieno[3,2-d]pyrimidine-2,4(1H,3H)-dione | |
| 0.000084 | - |
pH and temperature not specified in the publication | Human immunodeficiency virus 1 | 3-hydroxy-6-phenylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione | |
| 0.0001 | - |
pH and temperature not specified in the publication | Human immunodeficiency virus 1 | 3-hydroxy-1,5,6,7-tetrahydro-2H-cyclopenta[4,5]thieno[2,3-d]pyrimidine-2,4(3H)-dione | |
| 0.0001 | - |
pH and temperature not specified in the publication | Human immunodeficiency virus 1 | 3-hydroxy-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione | |
| 0.0001 | - |
pH and temperature not specified in the publication | Human immunodeficiency virus 1 | 3-hydroxy-5,6-dimethylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione | |
| 0.0001 | - |
pH and temperature not specified in the publication | Human immunodeficiency virus 1 | 3-hydroxy-5-methyl-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-6-carboxylic acid | |
| 0.0001 | - |
pH and temperature not specified in the publication | Human immunodeficiency virus 1 | 3-hydroxy-5-methylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione | |
| 0.0001 | - |
pH and temperature not specified in the publication | Human immunodeficiency virus 1 | 3-hydroxy-5-phenylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione | |
| 0.0001 | - |
pH and temperature not specified in the publication | Human immunodeficiency virus 1 | 3-hydroxy-6-phenylthieno [3,2-d]pyrimidine-2,4(1H,3H)-dione | |
| 0.0001 | - |
pH and temperature not specified in the publication | Human immunodeficiency virus 1 | 7-benzyl-3-hydroxy-5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione hydrochloride | |
| 0.0002 | - |
pH and temperature not specified in the publication | Human immunodeficiency virus 1 | 3-hydroxy-7-phenylquinazoline-2,4(1H,3H)-dione | |
| 0.0002 | - |
pH and temperature not specified in the publication | Human immunodeficiency virus 1 | 3-hydroxythieno[2,3-d]pyrimidine-2,4(1H,3H)-dione | |
| 0.0002 | - |
pH and temperature not specified in the publication | Human immunodeficiency virus 1 | 6-(4-fluorophenyl)-3-hydroxythieno[3,2-d]pyrimidine-2,4(1H,3H)-dione | |
| 0.0002 | - |
pH and temperature not specified in the publication | Human immunodeficiency virus 1 | 7-(4-chlorophenyl)-3-hydroxyquinazoline-2,4(1H,3H)-dione | |
| 0.0002 | - |
pH and temperature not specified in the publication | Human immunodeficiency virus 1 | 7-ethyl-3-hydroxy-5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione hydrochloride | |
| 0.0003 | - |
pH and temperature not specified in the publication | Human immunodeficiency virus 1 | 3-hydroxy-5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione hydrobromide | |
| 0.00033 | - |
pH and temperature not specified in the publication | Human immunodeficiency virus 1 | 7-benzyl-3-hydroxyhexahydropyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione hydrochloride | |
| 0.0013 | - |
pH and temperature not specified in the publication | Human immunodeficiency virus 1 | 2-hydroxy-6-phenylisoquinoline-1,3(2H,4H)-dione | |
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