Venomous animals produce venoms rich in hundreds of naturally occurring peptide toxins that provide a reservoir of potent receptor-binding agents. GPCRs are membrane proteins that control virtually all physiological processes. They are the target of 30% of the drugs currently in use. Many of these GPCRs are not exploited due to lack of effective and safe drugs. We specialize in exploring and exploiting venoms as a source of novel GPCR ligands. Our discovery process begins with venom deconvolution, screening, chemical synthesis, pharmacological characterization and in vivo validation. In addition, because venoms are complex mixtures, based on omic studies of 200 venomous animals, we have developed a unique synthetic library of natural toxins ready for screening. This library screened on 6 GPCRs gave an average success rate of 3%, 100 times higher than that obtained with artificial molecules, demonstrating the power of nature.
This presentation will focus not only on the discovery of toxins active on amine and peptide sensitive receptors, but also on how we turn incredible ligands into drug candidates. This process involves the selection of the therapeutic target, which must be related to medical needs, the in vivo validation of the targeted activity but also the evaluation of the safety of the toxin. The research conducted on the snake mambaquaretin toxin acting on the kidneys will illustrate this aspect. As the results were incredibly goods, we created the pharmaceutical company V4Cure, which will be in charge of the validating of the mambaquaretin activity in human.