GSK369796 Dihydrochloride (Synonyms: N-tert-butyl Isoquine)

Cell experiment:

Assays are performed in sterile 96-well microtiter plates, each plate contains 200 mL of parasite culture (2% parasitemia, 0.5% hematocrit) with or without 10 mL drug dilutions (including GSK369796 Dihydrochloride). Each drug is tested in triplicate and parasite growth is compared to control wells (which constitutes 100% parasite growth). Cultures are incubated for a further 24 h before they are harvested onto filter mats, dried for 1 h at 55 °C, and counted. IC50 values are calculated[1].

Animal experiment:

The efficacy of selected 4-aminoquinolines (including GSK369796 Dihydrochloride) is measured against P. yoelii or P. berghei in a 4-day test. 28 Cohorts of age-matched female mice are infected iv with 6.4×106 or 10.0×106 parasites obtained from infected donors, and the mice are randomly distributed in groups of n=5 mice/group (day 0). Treatments are administered from day 0 (one hour after infection) until day 3. The therapeutic efficacy of compounds (including GSK369796 Dihydrochloride) is expressed as the effective dose that reduces parasitemia by 50% (ED50) and 90% (ED90) with respect to vehicle treated groups (ED90) and the dose that achieved eradication of parasitemia until day 23 after infection (NRL). All compounds (including GSK369796 Dihydrochloride) and corresponding vehicles are administered orally at 20 mg/kg or subcutaneously at 10 mg/kg, as appropriate[1].

References:

[1]. O'Neill PM, et al. Candidate selection and preclinical evaluation of N-tert-butyl isoquine (GSK369796), an affordable and effective 4-aminoquinoline antimalarial for the 21st century. J Med Chem. 2009 Mar 12;52(5):1408-15.