TMECG

TMECG is a **prodrug designed for melanoma therapy** that is a trimethoxy derivative of (–)-epicatechin, a green tea polyphenol. It is selectively activated in melanoma cells by the enzyme **tyrosinase**, leading to the formation of a stable **quinone methide** (TMECG-QM) that **irreversibly inhibits dihydrofolate reductase (DHFR)**, a key enzyme in folate metabolism. Activated TMECG disrupts folate transport, downregulates DHFR expression, induces apoptosis, alters Bcl-2/Bax expression, and promotes caspase-3 activation in melanoma cells. The compound demonstrates high antiproliferative and proapoptotic activity in preclinical models and shows evidence of inhibiting melanoma tumor growth and metastasis, improving animal survival. Its dual mechanism also involves disruption of tetrahydrobiopterin recycling via H4B deficiency and superoxide production, potentially reducing nitric oxide bioavailability and enhancing hydrogen peroxide accumulation, which further contributes to the antitumor effect[1][2][3][4].

Other names

3-O-(3,4,5-trimethoxybenzoyl)-(-)-epicatechin