Unpacking the Pathogen Box-An Open Source Tool for Fighting Neglected Tropical Disease

ChemMedChem. 2019 Feb 19;14(4):386-453. doi: 10.1002/cmdc.201800755. Epub 2019 Jan 30.

Abstract

The Pathogen Box is a 400-strong collection of drug-like compounds, selected for their potential against several of the world's most important neglected tropical diseases, including trypanosomiasis, leishmaniasis, cryptosporidiosis, toxoplasmosis, filariasis, schistosomiasis, dengue virus and trichuriasis, in addition to malaria and tuberculosis. This library represents an ensemble of numerous successful drug discovery programmes from around the globe, aimed at providing a powerful resource to stimulate open source drug discovery for diseases threatening the most vulnerable communities in the world. This review seeks to provide an in-depth analysis of the literature pertaining to the compounds in the Pathogen Box, including structure-activity relationship highlights, mechanisms of action, related compounds with reported activity against different diseases, and, where appropriate, discussion on the known and putative targets of compounds, thereby providing context and increasing the accessibility of the Pathogen Box to the drug discovery community.

Keywords: Medicines for Malaria Venture; Pathogen Box; drug discovery; neglected tropical diseases.

Publication types

  • Review

MeSH terms

  • Agrochemicals / chemistry
  • Agrochemicals / therapeutic use*
  • Amides / chemistry
  • Amides / therapeutic use
  • Drug Discovery
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / therapeutic use
  • Farnesyl-Diphosphate Farnesyltransferase / antagonists & inhibitors
  • Humans
  • Metalloendopeptidases / antagonists & inhibitors
  • Neglected Diseases / drug therapy*
  • Neglected Diseases / pathology
  • Structure-Activity Relationship
  • Tubulin Modulators / chemistry
  • Tubulin Modulators / therapeutic use

Substances

  • Agrochemicals
  • Amides
  • Enzyme Inhibitors
  • Tubulin Modulators
  • Farnesyl-Diphosphate Farnesyltransferase
  • Metalloendopeptidases