RESUMEN
The 14th â Swiss Course on Medicinal Chemistry took place again in October 2022 in Leysin and provided a great opportunity for young medicinal chemists from diverse backgrounds for an intense and interactive week dedicated to the latest developments in drug design.
Asunto(s)
Química Farmacéutica , Descubrimiento de Drogas , Diseño de Fármacos , Suiza , HumanosRESUMEN
Solute carrier proteins (SLCs) are membrane proteins controlling fluxes across biological membranes and represent an emerging class of drug targets. Here we searched for inhibitors of divalent metal transporters in a library of 1,676 commercially available 3D-shaped fragment-like molecules from the generated database GDB-17, which lists all possible organic molecules up to 17â atoms of C, N, O, S and halogen following simple criteria for chemical stability and synthetic feasibility. While screening against DMT1 (SLC11A2), an iron transporter associated with hemochromatosis and for which only very few inhibitors are known, only yielded two weak inhibitors, our approach led to the discovery of the first inhibitor of ZIP8 (SLC39A8), a zinc transporter associated with manganese homeostasis and osteoarthritis but with no previously reported pharmacology, demonstrating that this target is druggable.