3,3',4,4'-tetrahydroxy-2-methoxychalcone

3,3',4,4'-Tetrahydroxy-2-methoxychalcone (TMC) is a bioactive chalcone and flavonoid compound isolated from the roots of *Glycyrrhiza uralensis* (licorice). It acts as a multi-target inhibitor that suppresses hypoxia-induced angiogenesis and modulates the neuroendocrine stress axis [EP1747]. TMC significantly reduces hypoxia-induced hypoxia-inducible factor-1 alpha (HIF-1α) protein accumulation via proteasome-dependent degradation, leading to decreased vascular endothelial growth factor (VEGF) expression. It also suppresses the Nrf2/HO-1 signaling pathway by reducing Nrf2 mRNA stability under hypoxic conditions. Preclinical studies in human colorectal cancer HCT-116 cells and human umbilical vein endothelial cells (HUVECs) demonstrate that TMC inhibits VEGF-induced migration, tube formation, and invasion, and attenuates VEGFR2 phosphorylation. Additionally, TMC modulates neuroendocrine stress responses by reducing hypoxia-induced increases in tyrosine hydroxylase (TH), corticotropin-releasing hormone (CRH), and endothelin-1 (ET-1) expression [EP1747]. It has also been identified as a selective Factor Xa inhibitor with potential anticoagulant properties.

Other names

(E)-3-(3,4-dihydroxy-2-methoxyphenyl)-1-(3,4-dihydroxyphenyl)prop-2-en-1-one3,3',4,4'-Tetrahydroxy-2-methoxychalconeTetrahydroxymethoxychalconeTMC