Terameprocol, a novel, semisynthetic derivative of a naturally occurring plant
lignan, is under development by Erimos
Pharmaceuticals LLC for the potential treatment of
cancer. The antitumor activity of
terameprocol is based on the selective inhibition of specificity
protein 1 (Sp1)-regulated
proteins, including
cyclin-dependent kinase 1,
survivin and
VEGF. With this mechanism of action,
terameprocol potentially inhibits the cell cycle, triggers apoptosis and decreases angiogenesis. Several preclinical studies have demonstrated the potent anticancer activity of
terameprocol in tumor cell lines and animal models. In addition,
terameprocol prevented the proliferation of HIV, HSV and HPV by a deactivation of viral Sp1-dependent promoters in preclinical studies. In a phase I clinical trial in patients (25 evaluable) with solid
tumors administered intravenous
terameprocol, 8 patients exhibited stable disease and 17 had progressive disease; the
drug was generally well tolerated. A good safety and efficacy profile has also been observed with the intratumoral and
intravaginal administration of
terameprocol in patients with head and neck or
squamous cell carcinoma and in patients with
cervical dysplasia, respectively. At the time of publication,
terameprocol was in phase I or I/II clinical development for the treatment of
glioma, treatment-refractory solid
tumors and
cervical dysplasia; a phase I clinical trial was also planned in patients with hematological
cancers. Thus, the favorable tolerability and efficacy profile demonstrated for
terameprocol to date suggests that the further investigation of this
drug is warranted.