|Awale Mahendra||Postdoctoral Fellow|
The NCCR TransCure screening facility provides the manpower, expertise and equipment required to develop and validate screening assays for diverse transporter targets. We help the PIs from the individual projects to upscale their assays in order to use them to evaluate small molecules in a typical medium-throughput format (<6’000 compounds) for primary target activity, and if required for selectivity studies. Compounds are provided from the chemistry groups either as targeted sets selected by virtual screening, from CROs, or as series of focused synthetic compounds generated in house or in collaboration with industry partners. Current project with links to the screening facility are LAT1, DMT1, endocannabinoid transport, OATP and TRPM4. In-house facilities for screening include basic 96-well robotics for compound handling if required; a FLIPR automated 96-well parallel fluorescence plate reader, plate washers, and a TopCount NXT 96-well scintillation counter. An extensive screening initiative has led to the optimization of TRPV6 calcium channel inhibitors vy using a 3D ligand-based virtual screening method.
Simonin C, Awale M, Brand M, van Deursen R, Schwartz J, Fine M, Kovacs G, Häfliger P, Gyimesi G, Sithampari A, Charles RP, Hediger MA, Reymond JL. (2015) Optimization of TRPV6 Calcium Channel Inhibitors Using a 3D Ligand-Based Virtual Screening Method. Angew Chem Int Ed Engl., doi: 10.1002/anie.201507320.