Abstract
Ivermectin is a gold standard antiparasitic drug that has been used successfully to treat billions of humans, livestock and pets. Until recently, the binding site on its Cys-loop receptor target had been a mystery. Recent protein crystal structures, site-directed mutagenesis data and molecular modelling now explain how ivermectin binds to these receptors and reveal why it is selective for invertebrate members of the Cys-loop receptor family. Combining this with emerging genomic information, we are now in a position to predict species sensitivity to ivermectin and better understand the molecular basis of ivermectin resistance. An understanding of the molecular structure of the ivermectin binding site, which is formed at the interface of two adjacent subunits in the transmembrane domain of the receptor, should also aid the development of new lead compounds both as anthelmintics and as therapies for a wide variety of human neurological disorders.
| Original language | English |
|---|---|
| Journal | Trends in Pharmacological Sciences |
| Volume | 33 |
| Issue number | 8 |
| Pages (from-to) | 432-41 |
| Number of pages | 10 |
| ISSN | 0165-6147 |
| DOIs | |
| Publication status | Published - Aug 2012 |
Keywords
- Amino Acid Sequence
- Animals
- Antiparasitic Agents
- Binding Sites
- Crystallography, X-Ray
- Cysteine Loop Ligand-Gated Ion Channel Receptors
- Humans
- Invertebrates
- Ivermectin
- Models, Molecular
- Molecular Sequence Data
- Mutagenesis, Site-Directed
- Protein Conformation