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Literature summary for 1.5.1.3 extracted from

  • Sanchez-del-Campo, L.; Tarraga, A.; Montenegro, M.F.; Cabezas-Herrera, J.; Rodriguez-Lopez, J.N.
    Melanoma activation of 3-o-(3,4,5-trimethoxybenzoyl)-(-)-epicatechin to a potent irreversible inhibitor of dihydrofolate reductase (2009), Mol. Pharm., 6, 883-894.
    View publication on PubMed

Cloned(Commentary)

Cloned (Comment) Organism
quantitative real-time PCR expression analysis of DHFR Homo sapiens

Inhibitors

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/ Products (Substrates)

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

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Source Tissue

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 and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
7,8-dihydrofolate + NADPH + H+
-
Homo sapiens 5,6,7,8-tetrahydrofolate + NADP+
-
?

Synonyms

Synonyms Comment Organism
DHFR
-
Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
25
-
assay at Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.4
-
assay at Homo sapiens

Cofactor

Cofactor Comment Organism Structure
NADPH
-
Homo sapiens

Ki Value [mM]

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

Expression

Organism Comment Expression
Homo sapiens 3-O-(3,4,5-trimethoxybenzoyl)-(-)-epicatechin efficiently downregulates melanoma DHFR expression down