Terameprocol (EM-1421) is a synthetic tetra-methylated derivative of nordihydroguaiaretic acid (NDGA) and transcriptional inhibitor with potential antiviral, antiangiogenic, and antineoplastic activities. Terameprocol showed the strongest anti-HIV activity.

In Vero cells, Terameprocol inhibited Sp1 transcription factor binding at the HIV long terminal repeat promoter and at the α-ICP4 promoter with IC50 values of 11 and 43.5 μM, respectively. The IC50 of Terameprocol varied between 11.7 and 4 μM in 10 passages of HSV-1 and 4 passages of HSV-2 [2]. Terameprocol inhibited Sp1-dependent Cdc2 gene expression. In M4N-treated transformed C3 cells, Terameprocol induced growth arrest and apoptosis by suppressing Sp1-dependent Cdc2 and survivin gene expression giving rise to its antitumorigenic activity [3]. Terameprocol treatment suppressed expression of the Sp1-dependent survivin gene. In transiently and stably survivin-transfected C3 cells, Terameprocol reduced caspase-3 activation by 50% and 75%, respectively [3]. Terameprocol inhibited the growth of a number of tumor cell lines by inducing apoptosis in a non-schedule-dependent manner [4]. Terameprocol inhibited the synthesis of DNA by melanoma cells and causes cell cycle arrest in G0/G1 and G2/M phases of the cell cycle [4].

Terameprocol effectively inhibited the growth of human tumors in nude mice [5]. Terameprocol inhibited the growth of both murine and human melanomas and human colon cancer without apparent hepatic or renal toxicity [4]. In nude (nu/nu) mice bearing xenografts of human tumor types (Hep 3B, LNCaP, HT-29, MCF7, and K-562), treatment with Terameprocol (i.v. or i.p.) down-regulated Cdc2 and survivin genes expression [5].