Tylosin analogs as antifilarials: Tom von Geldern
Tom von Geldern (AbbVIe/Franciscan Institute for World Health) talks about discovery of a novel macrofilaricidal agent, Tylosin A (TylA), which acts by targeting the worm-symbiont Wolbachia bacterium. This provides a new treatment for conditions such as river blindness and elephantiasis that affect large populations in Africa.
Chemical modification of TylA leads to improvements in anti-Wolbachia activity and oral pharmacokinetic properties; an optimized analog (ABBV-4083) has been selected for clinical evaluation. This webinar will describe the medicinal chemistry optimization program, and will give a snapshot of the preclinical characterization of the candidate, including in vivo profiling in the search for a new solution to treatment of onchocerciasis / loiasis co-infection, where mass drug administration is restricted. The compound is a natural product and Tom described some of the elegant synthetic chemistry required to selectively functionalist individual hydroxyls. The compounds will shortly go into Phase 2 clinical trials in collaboration with DNDi
