Terameprocol, a novel site-specific transcription inhibitor with anticancer activity

IDrugs. 2008 Mar;11(3):204-14.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / therapeutic use*
  • Clinical Trials as Topic
  • Humans
  • Masoprocol / analogs & derivatives*
  • Masoprocol / chemistry
  • Masoprocol / therapeutic use
  • Molecular Structure
  • Transcriptional Activation / drug effects*

Substances

  • Antineoplastic Agents
  • terameprocol
  • Masoprocol