PRECLINICAL REPORTSThe anticancer activity of the transcription inhibitor terameprocol (meso-tetra-O-methyl nordihydroguaiaretic acid) formulated for systemic administrationLopez, Rocio A.; Goodman, Amanda B.; Rhodes, Melissa; Blomberg, Jessica A.L.; Heller, JonathanAuthor Information Erimos Pharmaceuticals, Raleigh, North Carolina, USA Correspondence to Dr Rocio A. Lopez, Erimos Pharmaceuticals, 930 Main Campus Dr, Ste. 100, Raleigh, NC 27606, USA Tel: +1 919 821 5204 (ext) 2808; e-mail: firstname.lastname@example.org Received 18 December 2006 Accepted 25 February 2007 Anti-Cancer Drugs: September 2007 - Volume 18 - Issue 8 - p 933-939 doi: 10.1097/CAD.0b013e32813148e0 Buy Metrics Abstract Terameprocol (meso-tetra-O-methyl nordihydroguaiaretic acid, formerly known as EM-1421 and M4N) is a semi-synthetic small molecule with antitumor activity occurring via selective targeting of Sp1-regulated proteins, including survivin and cdc2 that control cell cycle and apoptosis. Terameprocol is in clinical development as a site-specific transcription inhibitor in solid refractory tumors. The present studies were designed to investigate the in-vitro and in-vivo anticancer activity of terameprocol in a novel hydroxypropyl β-cyclodextrin and polyethylene glycol solvent formulation (designated CPE) designed for safe parenteral administration. Terameprocol powder was dissolved in CPE (20% hydroxypropyl β-cyclodextrin and 50% polyethylene glycol 300 or 30% hydroxypropyl β-cyclodextrin and 25% polyethylene glycol 300) or dimethyl sulfoxide and used for in-vitro cell proliferation assays, and in human carcinoma xenograft studies using female athymic nude mice injected with SW-780 human bladder cells. Terameprocol (50 and 100 mg/kg), paclitaxel (5 mg/kg), terameprocol and paclitaxel or vehicle was administered intraperitoneally daily for 21 days. Stock solutions of the CPE formulation were stable for up to 12 months. Terameprocol CPE formulation showed concentration-dependent inhibition of HeLa and C33A cell proliferation, and was less toxic than terameprocol dimethyl sulfoxide formulation. The terameprocol CPE formulation showed no overt toxicities in tumor-bearing mice. Terameprocol alone reduced the rate of tumor growth, and a combination of terameprocol/paclitaxel reduced both the rate and extent of tumor growth. These preclinical results confirm the tumoricidal activity of terameprocol formulated in a solvent suitable for parenteral administration and suggest that terameprocol has improved efficacy when coadministered with paclitaxel. © 2007 Lippincott Williams & Wilkins, Inc.