Structure-guided screening of FAR-1 antagonists with multi-stage anthelmintic activity
Juan Wen1, Wenmin Qi1, Jinwei Lv1
1State Key Laboratory of Animal Disease Control and Prevention, Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong, China.
Antimicrobial Agents and Chemotherapy
|April 15, 2026
Summary
Fatty acid and retinol binding proteins (FARs) are crucial for nematode survival. Researchers identified novel drug candidates targeting FAR-1, showing significant efficacy against parasitic worms in mouse models with minimal toxicity.
Area of Science:
- Parasitology
- Drug Discovery
- Biochemistry
Background:
- Fatty acid and retinol binding proteins (FARs) are nematode-specific proteins essential for lipid metabolism and development.
- FARs play a role in host immune response modulation, making them potential targets for anthelmintic drugs.
Purpose of the Study:
- To identify antagonists of *Nippostrongylus brasiliensis* FAR-1 (NbFAR-1) as potential anthelmintic drug leads.
- To evaluate the efficacy and safety of identified compounds against parasitic nematodes in vitro and in vivo.
Main Methods:
- Integrated virtual screening, fluorescent ligand binding assays, and in vitro egg hatching assays were used to identify NbFAR-1 antagonists.
- An in vivo mouse model was employed to assess anthelmintic efficacy against *N. brasiliensis* and *Angiostrongylus cantonensis*.
Main Results:
- Six compounds demonstrated significant antagonism to NbFAR-1 and suppressed *N. brasiliensis* egg hatching.
- Two candidates, E002-0872 and 4340-0245, effectively reduced intestinal *N. brasiliensis* burdens and associated damage in mice.
- Compound 4340-0245 also reduced cerebral *A. cantonensis* burdens, alleviated neurological signs, and showed favorable pharmacokinetic properties without significant toxicity.
Conclusions:
- FAR-1 is a promising drug target for developing novel anthelmintic therapies.
- The identified compound 4340-0245 demonstrates significant potential as an anthelmintic agent against multiple nematode infections.
