Toxicity and efficacy of benzamide riboside in cancer chemotherapy models

Hiremagalur N. Jayaram, Joel A. Yalowitz, Francisco Arguello, John F. Greene

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Benzamide riboside (BR), a synthetic C-nucleoside, acts as a strong growth inhibitor of cancer cells in vitro and in vivo. BR, like TR and related nucleoside prodrugs, act by anabolism to NAD analogs. These analogs selectively inhibit IMPDH, leading to depletion of cellular GTP, growth cessation, and cell differentiation. To date only preclinical studies have been carried out. However, in tiazofurin (TR), a related drug, phase I/II clinical trials have been conducted in patients with acute leukemia and shown to be a very promising agent with a response rate of 85% in 26 patients in one of the trials. Tiazofurin is now undergoing phase III clinical trials as a result. Dose limiting toxicity of tiazofurin was headache, somnolence and nausea with no myelosuppression noted. By contrast, BR showed skeletal muscle toxicity, hepatotoxicity and myelosuppression in preclinical data. Skeletal muscle toxicity was noted in the paraspinal muscles and may represent dose-limiting toxicity. Since BR does exhibit myelosuppression, the most common chemotherapy-related side effect in humans, careful judgment is warranted should BR be included in multidrug regimens, although BR's potent cytotoxicity to tumor cells in preclinical models still makes it a promising drug.

Original languageEnglish (US)
Pages (from-to)787-792
Number of pages6
JournalCurrent Medicinal Chemistry
Volume9
Issue number7
DOIs
StatePublished - Jan 1 2002

Keywords

  • Apoptosis
  • Benzamide riboside
  • Cancer chemotherapy
  • Preclinical evaluation
  • Toxicity

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Fingerprint Dive into the research topics of 'Toxicity and efficacy of benzamide riboside in cancer chemotherapy models'. Together they form a unique fingerprint.

  • Cite this