Biological Evaluation of Compounds

 

A p.o. P.Berghei mouse study at 50 mg/kg revealed no efficacy of OSM-S-35 (ZYH 3-1),OSM-S-5 (TCMDC-123812) or OSM-S-6 (TCMDC-123794) relative to control. Experiments carried out at Swiss TPH. Experiment start 23/04/12.



Method Overview:
"This protocol is performed in the group of Dr Sergio Wittlin at Swiss TPH (Unit of Prof. Reto Brun), for assessing compound efficacy against the Plasmodium berghei GFP ANKA strain in-vivo. Mice are infected intravenously with parasitized red blood cells on day 0 (2 x 107 parasitized erythrocytes per ml). Experimental mice are generally treated at 4, 24, 48, and 72 hours post-infection with an oral dose of the compound (4-day test by Peters) and are compared to an infected control group for reduction in parasitaemia on day 4 (96 hours post-infection) in % and for mean survival (monitored up to 30 days post-infection). A compound is considered curative, if the animal survives to day 30 after infection with no detectable parasites. Other delivery route (intravenous, intraperitoneal, subcutaneous) and dosing regimen (e.g. single dose) are possible.

Percent activities below 40% are regarded as inactive.

To put the data into context, a new lead optimization project should typically show an oral ED50 <50mg/kg while a development candidate will typically have an oral ED90 <10mg/kg"

The raw data in excel format: