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Peer-reviewed veterinary case report

Substituted imidazopyridazines are potent and selective inhibitors of Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1).

Journal:
Bioorganic & medicinal chemistry letters
Year:
2013
Authors:
Chapman, Timothy M et al.
Affiliation:
Centre for Therapeutics Discovery · United Kingdom

Abstract

A series of imidazopyridazines which are potent inhibitors of Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1) was identified from a high-throughput screen against the isolated enzyme. Subsequent exploration of the SAR and optimisation has yielded leading members which show promising in vitro anti-parasite activity along with good in vitro ADME and selectivity against human kinases. Initial in vivo testing has revealed good oral bioavailability in a mouse PK study and modest in vivo efficacy in a Plasmodium berghei mouse model of malaria.

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Original publication: https://pubmed.ncbi.nlm.nih.gov/23570789/