Activity of epigenetic inhibitors against Babesia divergens.
Vanheer, L. N.; Kafsack, B. F. C.
Show abstract
Babesiosis in a tick-borne parasitic disease of humans and livestock, that has dramatically increased in frequency and geographical range over the past few decades. Infection of cattle often causes large economic losses, and human infection can be fatal in immunocompromised patients. Unlike for malaria, another disease caused by hemoprotozoan parasites, limited treatment options exist for Babesia infections. As epigenetic regulation is a promising target for new anti-parasitic drugs, we screened 324 epigenetic inhibitors against Babesia divergens blood stages and identified 75 (23%) and 17 (5%) compounds that displayed [≥]90% inhibition at 10 {micro}M and 1 {micro}M, respectively, including over a dozen compounds with activity in the low nanomolar range. We observed differential activity of some inhibitor classes against Babesia divergens and Plasmodium falciparum parasites and identified pairs of compounds with a high difference in activity, despite a high similarity in chemical structure, highlighting new insights into the development of epigenetic inhibitors as anti-parasitic drugs.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- A pyridyl-furan series developed from Open Global Health Library blocks red blood cell invasion and protein trafficking in Plasmodium falciparum through potential inhibition of the parasites PI4KIIIb enzyme. 96%
- Mammalian deubiquitinating enzyme inhibitors display in vitro and in vivo activity against malaria parasites and potentiate artemisinin action 96%
- High-throughput screening of more than 30,000 compounds for anthelmintics against gastrointestinal nematode parasites 96%
Similar papers in this journal
- A Survey of the Kinome Pharmacopeia Reveals Multiple Scaffolds and Targets for the Development of Novel Anthelmintics 93%
- HTRF-based identification of small molecules targeting SARS-CoV-2 E protein interaction with ZO-1 PDZ2 93%
- Identification of kinase inhibitors as potential host-directed therapies for intracellular bacteria 93%
Similar papers in this journal
- Identification of an inhibitory pocket in falcilysin provides a new avenue for malaria drug development 95%
- Mixed Alkyl/Aryl Phosphonates Identify Metabolic Serine Hydrolases as Antimalarial Targets 93%
- The antimalarial natural product salinipostin A identifies essential α/β serine hydrolases involved in lipid metabolism in P. falciparum parasites 93%
Similar papers in this journal
- Collateral sensitivity as a strategy to suppress resistance emergence: the challenge of diverse evolutionary pathways 94%
- Development of antibacterial compounds that block evolutionary pathways to resistance 92%
- A single point mutation in the Plasmodium falciparum ftsh1 metalloprotease confers actinonin resistance. 92%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.