Cloned (Comment) | Organism |
---|---|
quantitative real-time PCR expression analysis of DHFR | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
3-O-(3,4,5-trimethoxybenzoyl)-(-)-epicatechin | i.e. TMECG, synthesis of a trimethoxy derivative of epicatechin-3-gallate, which shows high antiproliferative and proapoptotic activity against melanoma. It is a prodrug that is selectively activated by the specific melanocyte enzyme tyrosinase. Upon activation, the compound generates a stable quinone methide product that strongly inhibits dihydrofolate reductase in an irreversible manner. The treatment of melanoma cells affects cellular folate transport and the gene expression of DHFR | Homo sapiens | |
epicatechin-3-O-gallate | - |
Homo sapiens | |
epigallocatechin-3-O-gallate | - |
Homo sapiens | |
quinone methide | essentially irreversible inhibition | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
7,8-dihydrofolate + NADPH + H+ | Homo sapiens | - |
5,6,7,8-tetrahydrofolate + NADP+ | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
melanoma cell | DHFR is overexpressed in melanoma cells | Homo sapiens | - |
SK-MEL-28 cell | DHFR is overexpressed in SkMel-28 melanoma cells | Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
7,8-dihydrofolate + NADPH + H+ | - |
Homo sapiens | 5,6,7,8-tetrahydrofolate + NADP+ | - |
? |
Synonyms | Comment | Organism |
---|---|---|
DHFR | - |
Homo sapiens |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
25 | - |
assay at | Homo sapiens |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7.4 | - |
assay at | Homo sapiens |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
NADPH | - |
Homo sapiens |
Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
---|---|---|---|---|---|
additional information | - |
additional information | stopped-flow inhibition kinetics, molecular modeling, overview | Homo sapiens | |
0.0000082 | - |
quinone methide | pH 7.4, 25°C | Homo sapiens | |
0.00092 | - |
epigallocatechin-3-O-gallate | pH 7.4, 25°C | Homo sapiens | |
0.00178 | - |
epicatechin-3-O-gallate | pH 7.4, 25°C | Homo sapiens | |
0.0021 | - |
3-O-(3,4,5-trimethoxybenzoyl)-(-)-epicatechin | pH 7.4, 25°C | Homo sapiens |
Organism | Comment | Expression |
---|---|---|
Homo sapiens | 3-O-(3,4,5-trimethoxybenzoyl)-(-)-epicatechin efficiently downregulates melanoma DHFR expression | down |