tetramethyl Nordihydroguaiaretic acid (TMNDGA) is a synthetic derivative of NDGA, a non-selective lipoxygenase inhibitor. It inhibits Sp1 transcription factor binding at the HIV long terminal repeat promoter and at the α-ICP4 promoter, a gene essential for HSV replication, with IC50 values of 11 and 43.5 μM respectively TMNDGA induces growth arrest and apoptosis by suppressing Sp1-dependent Cdc2 and survivin gene expression giving rise to its antitumorigenic activity. The in vivo growth of xenografts in numerous human tumor types was suppressed upon treatment with TMNDGA. It also inhibits the growth of mouse and human melanomas and human colon cancer in vivo without causing other tissue toxicity. TMNDGA is currently in Phase I & II clinical trials for treatment of high grade glioma brain tumors.
