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Literature summary for 3.6.1.9 extracted from
- Synthesis, biological evaluation, and docking studies of new raloxifene sulfonate or sulfamate derivatives as inhibitors of nucleotide pyrophosphatase/phosphodiesterase (2019), Eur. J. Med. Chem., 181, 111560 .
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| 2-[4-[(4-fluorobenzene-1-sulfonyl)oxy]phenyl]-3-[4-[2-(piperidin-1-yl)ethoxy]benzoyl]-1-benzothiophen-6-yl 4-fluorobenzene-1-sulfonate | - |
Homo sapiens |  |
| 2-[4-[(4-methoxybenzene-1-sulfonyl)oxy]phenyl]-3-[4-[2-(piperidin-1-yl)ethoxy]benzoyl]-1-benzothiophen-6-yl 4-methoxybenzene-1-sulfonate | - |
Homo sapiens | |
| 2-[4-[(4-methylbenzene-1-sulfonyl)oxy]phenyl]-3-[4-[2-(piperidin-1-yl)ethoxy]benzoyl]-1-benzothiophen-6-yl 4-methylbenzene-1-sulfonate | 38.5% inhibition | Homo sapiens | |
| 2-[4-[(4-tert-butylbenzene-1-sulfonyl)oxy]phenyl]-3-[4-[2-(piperidin-1-yl)ethoxy]benzoyl]-1-benzothiophen-6-yl 4-tert-butylbenzene-1-sulfonate | shows cytotoxicity against MCF-7 and HT-29 cell lines and shows less cytotoxicity on against A-549 cell | Homo sapiens | |
| 2-[4-[(cyclohexanesulfonyl)oxy]phenyl]-3-[4-[2-(piperidin-1-yl)ethoxy]benzoyl]-1-benzothiophen-6-yl cyclohexanesulfonate | 30.0% inhibition | Homo sapiens | |
| 2-[4-[(dimethylsulfamoyl)oxy]phenyl]-3-[4-[2-(piperidin-1-yl)ethoxy]benzoyl]-1-benzothiophen-6-yl dimethylsulfamate | 43.7% inhibition | Homo sapiens | |
| 2-[4-[(ethanesulfonyl)oxy]phenyl]-3-[4-[2-(piperidin-1-yl)ethoxy]benzoyl]-1-benzothiophen-6-yl ethanesulfonate | 35.1% inhibition | Homo sapiens | |
| 2-[4-[(methylsulfamoyl)oxy]phenyl]-3-[4-[2-(piperidin-1-yl)ethoxy]benzoyl]-1-benzothiophen-6-yl methylsulfamate | 36.0% inhibition | Homo sapiens | |
| 4-(3-[4-[2-(piperidin-1-yl)ethoxy]benzoyl]-6-[(quinoline-8-sulfonyl)oxy]-1-benzothiophen-2-yl)phenyl quinoline-8-sulfonate | 28.7 inhibition; 42.5% inhibition | Homo sapiens | |
| 4-(3-[4-[2-(piperidin-1-yl)ethoxy]benzoyl]-6-[[4-(trifluoromethyl)benzene-1-sulfonyl]oxy]-1-benzothiophen-2-yl)phenyl 4-(trifluoromethyl)benzene-1-sulfonate | - |
Homo sapiens | |
| additional information | a series of raloxifene sulfonate/sulfamate derivatives are designed, synthesized, and tested for inhibitory effect against nucleotide pyrophosphatase/phosphodiesterase-1 and -3 (NPP1 and NPP3) enzymes. The compounds are subjected to cytotoxic studies on various cancer cell lines, and the most potent derivatives are explored for their potency against these cancer cell lines, e.g. HT-29 cells, as well as F180 fibroblasts, inhibition values in percent per 0.01 mM. Structure-activity relationships, molecular modeling of inhibitor binding, overview. Pi-Pi stacking interactions and metal interactions with zinc inside the active site are noticed and contributed towards the inhibitory activity; a series of raloxifene sulfonate/sulfamate derivatives are designed, synthesized, and tested for inhibitory effect against nucleotide pyrophosphatase/phosphodiesterase-1 and -3 (NPP1 and NPP3) enzymes. The compounds are subjected to cytotoxic studies on various cancer cell lines, and the most potent derivatives are explored for their potency against these cancer cell lines, e.g. HT-29 cells, as well as F180 fibroblasts. Structure-activity relationships, molecular modeling of inhibitor binding, overview. Pi-Pi stacking interactions and metal interactions with zinc inside the active site are noticed and contributed towards the inhibitory activity | Homo sapiens |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| membrane | - |
Homo sapiens | 16020 | - |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Mg2+ | required | Homo sapiens | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | O14638 | - |
- |
| Homo sapiens | P22413 | - |
- |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| A-549 cell | - |
Homo sapiens | - |
| colonic cancer cell | - |
Homo sapiens | - |
| F180 cell | - |
Homo sapiens | - |
| fibroblast | - |
Homo sapiens | - |
| HT-29 cell | - |
Homo sapiens | - |
| MCF-7 cell | - |
Homo sapiens | - |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| E-NPP1 | - |
Homo sapiens |
| E-NPP3 | - |
Homo sapiens |
| NPP1 | - |
Homo sapiens |
| NPP3 | - |
Homo sapiens |
| nucleotide pyrophosphatase/phosphodiesterase | - |
Homo sapiens |
Temperature Optimum [°C]
| Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
|---|---|---|---|
| 37 | - |
assay at | Homo sapiens |
pH Optimum
| pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|
| 9.5 | - |
assay at | Homo sapiens |
IC50 Value
| IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
|---|---|---|---|---|---|
| 0.00023 | - |
pH 9.5, 37°C | Homo sapiens | 4-(3-[4-[2-(piperidin-1-yl)ethoxy]benzoyl]-6-[[4-(trifluoromethyl)benzene-1-sulfonyl]oxy]-1-benzothiophen-2-yl)phenyl 4-(trifluoromethyl)benzene-1-sulfonate | |
| 0.00029 | - |
pH 9.5, 37°C | Homo sapiens | 2-[4-[(4-tert-butylbenzene-1-sulfonyl)oxy]phenyl]-3-[4-[2-(piperidin-1-yl)ethoxy]benzoyl]-1-benzothiophen-6-yl 4-tert-butylbenzene-1-sulfonate | |
| 0.00042 | - |
pH 9.5, 37°C | Homo sapiens | 2-[4-[(4-methoxybenzene-1-sulfonyl)oxy]phenyl]-3-[4-[2-(piperidin-1-yl)ethoxy]benzoyl]-1-benzothiophen-6-yl 4-methoxybenzene-1-sulfonate | |
| 0.00045 | - |
pH 9.5, 37°C | Homo sapiens | 2-[4-[(4-methylbenzene-1-sulfonyl)oxy]phenyl]-3-[4-[2-(piperidin-1-yl)ethoxy]benzoyl]-1-benzothiophen-6-yl 4-methylbenzene-1-sulfonate | |
| 0.00049 | - |
pH 9.5, 37°C | Homo sapiens | 2-[4-[(cyclohexanesulfonyl)oxy]phenyl]-3-[4-[2-(piperidin-1-yl)ethoxy]benzoyl]-1-benzothiophen-6-yl cyclohexanesulfonate | |
| 0.00071 | - |
pH 9.5, 37°C | Homo sapiens | 2-[4-[(4-tert-butylbenzene-1-sulfonyl)oxy]phenyl]-3-[4-[2-(piperidin-1-yl)ethoxy]benzoyl]-1-benzothiophen-6-yl 4-tert-butylbenzene-1-sulfonate | |
| 0.00124 | - |
pH 9.5, 37°C | Homo sapiens | 2-[4-[(4-methoxybenzene-1-sulfonyl)oxy]phenyl]-3-[4-[2-(piperidin-1-yl)ethoxy]benzoyl]-1-benzothiophen-6-yl 4-methoxybenzene-1-sulfonate | |
| 0.00151 | - |
pH 9.5, 37°C | Homo sapiens | 2-[4-[(ethanesulfonyl)oxy]phenyl]-3-[4-[2-(piperidin-1-yl)ethoxy]benzoyl]-1-benzothiophen-6-yl ethanesulfonate | |
| 0.00155 | - |
pH 9.5, 37°C | Homo sapiens | 2-[4-[(methylsulfamoyl)oxy]phenyl]-3-[4-[2-(piperidin-1-yl)ethoxy]benzoyl]-1-benzothiophen-6-yl methylsulfamate | |
| 0.00181 | - |
pH 9.5, 37°C | Homo sapiens | 2-[4-[(4-fluorobenzene-1-sulfonyl)oxy]phenyl]-3-[4-[2-(piperidin-1-yl)ethoxy]benzoyl]-1-benzothiophen-6-yl 4-fluorobenzene-1-sulfonate | |
| 0.00401 | - |
pH 9.5, 37°C | Homo sapiens | 4-(3-[4-[2-(piperidin-1-yl)ethoxy]benzoyl]-6-[[4-(trifluoromethyl)benzene-1-sulfonyl]oxy]-1-benzothiophen-2-yl)phenyl 4-(trifluoromethyl)benzene-1-sulfonate | |
| 0.00888 | - |
pH 9.5, 37°C | Homo sapiens | 2-[4-[(4-fluorobenzene-1-sulfonyl)oxy]phenyl]-3-[4-[2-(piperidin-1-yl)ethoxy]benzoyl]-1-benzothiophen-6-yl 4-fluorobenzene-1-sulfonate | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| evolution | nucleotide pyrophosphatase/phosphodiesterase (NPP) enzymes belong to the alkaline phosphatase superfamily, with active site characterized by residues of histidine centrally coordinated by divalent cations and serine, cysteine, or threonine residues | Homo sapiens |
| additional information | the active site of NPP1 includes several amino acids such as Ser343, Thr256, Lys295, Phe346, Phe257, Asn277, Tyr340, Lys295, Glu373, Asp376, Tyr451, and His380, they are involved in significant interactions | Homo sapiens |
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