bms-387032 and Haemonchiasis

In partnership with the Medicines for Malaria Venture (MMV), we screened a collection ('Stasis Box') of 400 compounds (which have been in clinical development but have not been approved for illnesses other than neglected infectious diseases) for inhibitory activity against Haemonchus contortus, in order to attempt to repurpose some of the compounds to parasitic nematodes.. We assessed the inhibition of compounds on the motility and/or development of exsheathed third-stage (xL3s) and fourth-stage (L4) larvae of H. contortus using a whole-organism screening assay.. Although the two kinase inhibitors, SNS-032 and AG-1295, had moderate inhibitory activity on the motility or development of xL3s or L4s of H. contortus in vitro, further work needs to be undertaken to chemically alter these entities to achieve the potency and selectivity required for them to become nematocidal or nematostatic candidates.

Topics: Amino Acid Sequence; Animals; Antinematodal Agents; Cell Line; Dose-Response Relationship, Drug; Haemonchiasis; Haemonchus; Humans; Larva; Models, Molecular; Oxazoles; Protein Kinase Inhibitors; Sequence Alignment; Small Molecule Libraries; Thiazoles; Tyrphostins