From antiparasitic to anticancer: DDD exit project explores new treatment strategies for cancer and lupus
A Drug Discovery and Development (DDD) Platform exit project at SciLifeLab has followed the scientific journey of an established antiparasitic drug towards new potential applications in cancer and autoimmune diseases.
The project, led by Peter Nygren, Mårten Fryknäs, and Rolf Larsson at Uppsala University, originated from an unexpected observation that the antiparasitic drug mebendazole showed effects in cancer models. Supported by the SciLifeLab Drug Discovery and Development (DDD) platform, the researchers combined clinical oncology, medicinal chemistry, in vitro profiling and experimental pharmacology to explore and advance this finding in depth.
A key challenge was the compound’s poor pharmacokinetic profile, which limited its clinical use. To address this, the team developed a prodrug version of mebendazole designed to improve its bioavailability and pharmacodynamic properties. The new prodrugs were generated in close collaboration with the DDD platform, including medicinal chemistry, ADME profiling, and in vivo pharmacokinetic evaluations.
In parallel, mechanistic studies were performed to clarify how the substance exerts its biological effects, using a combination of biochemical assays, cellular models, and pharmacological profiling by the Clinical Proteomics Mass Spectrometry Core Facility at SciLifeLab, Solna. These efforts led to the identification of a mechanism that may explain mebendazole’s effects in both cancer and autoimmune pathways, providing new insight into its mode of action and potential therapeutic use.
The project illustrates how drug repurposing, combined with interdisciplinary collaboration and innovative chemistry to overcome pharmacological limitations, can open novel avenues for therapeutic development.
“The multifaceted support from the DDD platform to move our project forward and now ending up with a promising prodrug has been invaluable”, Peter Nygren says.
Mårten Fryknäs adds, “Clinical Proteomics Mass Spectrometry facility finally provided the clue to how our drug works and this adds considerably to the possibilities to make project progress following our exit.”
