Novel insight into drug repositioning: Methylthiouracil as a case in point

Pharmacol Res. 2015 Sep:99:185-93. doi: 10.1016/j.phrs.2015.06.008. Epub 2015 Jun 25.

Abstract

Drug repositioning refers to the development of existing drugs for new indications. These drugs may have (I) failed to show efficacy in late stage clinical trials without safety issues; (II) stalled in the development for commercial reasons; (III) passed the point of patent expiry; or (IV) are being explored in new geographic markets. Over the past decade, pressure on the pharmaceutical industry caused by the 'innovation gap' owing to rising development costs and stagnant product output have become major reasons for the growing interest in drug repositioning. Companies that offer a variety of broad platforms for identifying new indications have emerged; some have been successful in building their own pipelines of candidates with reduced risks and timelines associated with further clinical development. The business models and platforms offered by these companies will be validated if they are able to generate positive proof-of-concept clinical data for their repositioned compounds. This review describes the strategy of biomarker-guided repositioning of chemotherapeutic drugs for inflammation therapy, considering the repositioning of methylthiouracil (MTU), an antithyroid drug, as a potential anti-inflammatory reagent.

Keywords: Anti-inflammatory reagent; Drug repositioning; Methylthiouracil; sPLA(2)-IIA.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Antithyroid Agents / pharmacology
  • Arthritis, Rheumatoid / drug therapy
  • Biomarkers / analysis
  • Doxycycline / pharmacology
  • Drug Discovery
  • Drug Repositioning / methods*
  • Drug Repositioning / trends
  • Erythema Nodosum / drug therapy
  • Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Intellectual Property
  • Leprosy, Lepromatous / drug therapy
  • Methylthiouracil / pharmacology*
  • Periodontitis / drug therapy
  • Phospholipases A2, Secretory / antagonists & inhibitors
  • Thalidomide / pharmacology
  • Vasculitis / drug therapy

Substances

  • Anti-Inflammatory Agents
  • Antithyroid Agents
  • Biomarkers
  • Thalidomide
  • Extracellular Signal-Regulated MAP Kinases
  • Phospholipases A2, Secretory
  • Doxycycline
  • Methylthiouracil