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Infectious disease


Platelet factor 4 (PF4; CXCL4)

In vitro and mouse studies suggest small molecule mimetics of PF4 could help treat malaria. In vitro, the host defense peptide PF4 induced lysis of the Plasmodium falciparum digestive vacuole at low micromolar concentrations. A screen of small molecule host defense peptide mimetics identified a compound that killed P. falciparum at low nanomolar concentrations. In a mouse model of malaria, i.v. injection of a lead mimetic decreased parasite load and increased survival compared with vehicle injection. Next steps include increasing the oral bioavailability of the compounds.
The study was carried out in collaboration with PolyMedix Inc., which has antimalarial host defense peptide mimetics in preclinical development.

SciBX 6(2); doi:10.1038/scibx.2013.36
Published online Jan. 17, 2013

Patent application filed; licensing status undisclosed

Love, M.S. et al. Cell Host Microbe; published online Dec. 13, 2012;
Contact: Doron C. Greenbaum, University of Pennsylvania, Philadelphia, Pa.