University of Georgia

Start : July 2016 | Status : Active

The scientist: Dr. Alba Gigante is an organic/ medicinal chemist by training, with experience working in neglected diseases. Currently she is a Postdoctoral Researcher working with Prof. Rick Tarleton from the University of Georgia.  Her primary role in this project is to identify novel phenotypic leads against Trypanosoma cruzi from the TCAKS_CHAGAS set (Tres Cantos Anti Kinetoplastid Set).  During her stay in Tres Cantos she will perform analog searches within GSK library for the in vivo active hits as well as the design of convergent synthetic routes for further SAR enrichment.

The sponsor: University of Georgia

Foundation funding: The Foundation is providing £189,705 in support.

GSK’s contribution: GSK will contribute with solid availability for compounds in the TCAKS_CHAGAS set (Tres Cantos Anti Kinetoplastid Set) as well as analogue searching within the GSK collection. GSK will contribute in-kind its drug discovery expertise supporting the design of new analogues as well as completing preliminary compound profiling (in vitro T.cruzi, in vitro ADMET)

Project Description: T. cruzi is a protozoan parasite that causes Chagas disease, the highest impact infectious disease in Latin America. Previous work at Tres Cantos has identified a total of 222 small molecule prioritized according to their potency against T.cruzi, cytotoxicity, and physico-chemical properties, called TCAKS-Chagas. The purpose of this project is to determine which among these prioritized in vitro-active compounds also has substantial in vivo activity on T. cruzi, and thus promise as a hit for lead compound development. 
The investigators from University of Georgia, led by Prof. Rick L. Tarleton, have developed a facile and rapid assay that makes use of transgenic T. cruzi lines expressing fluorescent proteins, which allows imaging the establishment and expansion of these tagged parasites after a single administration of compound, and hence determine in vivo efficacy of a number of compounds (up to 30 at a time) in < 1 week.  This rapid in vivo assay seems to be an excellent predictor of long-term efficacy and is thus a potent screening method for selection of candidates for subsequent studies.