1. Novartis Centre de Recherche Santé Animale, CH-1566 St Aubin (FR), Switzerland
2. Novartis Animal Health Inc., CH-4002 Basel, Switzerland
3. Cambria Biosciences, Woburn, Massachusetts 01801, USA
4. Institute of Cell Biology, University of Bern, CH-3012 Bern, Switzerland
5. Laboratoire Central Vétérinaire de Bingerville, BP 206, Lanada, Côte d'Ivoire

Correspondence to: Ronald Kaminsky¹ Correspondence and requests for materials should be addressed to R.K. (Email: ronald.kaminsky@novartis.com).

Abstract

Anthelmintic resistance in human and animal pathogenic helminths has been spreading in prevalence and severity to a point where multidrug resistance against the three major classes of anthelmintics—the benzimidazoles, imidazothiazoles and macrocyclic lactones—has become a global phenomenon in gastrointestinal nematodes of farm animals. Hence, there is an urgent need for an anthelmintic with a new mode of action. Here we report the discovery of the amino-acetonitrile derivatives (AADs) as a new chemical class of synthetic anthelmintics and describe the development of drug candidates that are efficacious against various species of livestock-pathogenic nematodes. These drug candidates seem to have a novel mode of action involving a unique, nematode-specific clade of acetylcholine receptor subunits. The AADs are well tolerated and of low toxicity to mammals, and overcome existing resistances to the currently available anthelmintics.

MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated.